ISSN (Print): 1570-159X
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Volume 19, 12 Issues, 2021
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Neurological disorders have been recognized by the World Health Organization (WHO) as a significant cause of the global burden of disease
worldwide, with the highest burden in low to middle-income countries, and this burden is expected to increase exponentially in the next decade
. Global burden of disease study has shown that mental, neurological, and substance use disorders are a significant cause of disability in the
global population [2-4]. Notably, the burden of neurological diseases in low- and middle-income countries is over six times higher than in developed
countries, with epilepsy being 14-fold higher, cerebrovascular disease being eight-fold higher, and migraines being six-fold higher [1, 5].
Therefore, there is a need to explore all possible interventions to help combat these diseases.
Many cultures worldwide primarily use herbs for health care needs  and for the treatment of conditions involving central nervous system
disorders, even though conventional medical treatments have been widely adopted. Many herbs are claimed to possess anticonvulsant, antiepileptic,
neuroprotective, memory-enhancing, and sedative properties; however, only some of these claims are supported by clinical data or experimental
results . This special issue of Current Neuropharmacology presents the state of knowledge as it relates to botanicals/herbs with neuroactive
properties. It also provides proposals for additional research to better understand their efficacy and safety profiles with the hope of stimulating
further research in the discovery of future medicines.
In the first review article, Choo and Shaikh examined the use of Curcuma longa (turmeric) and its constituents in the management of epileptic
seizures. C. longa is a tropical herbaceous perennial plant of the family Zingiberaceae. Its rhizome contains curcuminoids, sesquiterpenoids, and
monoterpenoids as the major constituents . C. longa is used traditionally as a remedy for epilepsy . The review determined that only nonclinical
studies were available reporting the use of an aqueous extract of C. longa rhizome and its oil, as well as the use of its major constituents:
curcumin and bisabolene sesquiterpenoids. Based on the reviewed data, the authors have suggested possible treatment parameters for epileptic
seizures and hypothesized possible mechanisms of action for the bioactive constituents. The authors also propose future research to support possible
drug development. The review recognizes the low bioavailability of curcumin, indicating that higher doses would be required to achieve
therapeutic levels . Based on studies reviewed, the most favorable route of administration would be intraperitoneal, which is not conventionally
used clinically. The review also recognized that the half-life of curcumin varies significantly between animal species, but overall is short, indicating
rapid metabolism, which the authors consider not necessarily a negative attribute given that metabolites may be therapeutically bioactive.
Lastly, the review stated that different formulations of curcumin may incorporate compounds, like piperine or synthetic analogues of curcumin, to
help overcome bioavailability and degradation issues . The authors propose the following possible mechanisms of action for neural activity:
antioxidant effects, anti-inflammatory effects, improved cognition, neuroprotective effects, modulation of neurotransmitter signals, downregulation
of sodium ion channels, and downregulation of cortisone. This review has unveiled an obvious gap as no clinical studies on C. longa
for the management of epileptic seizures are available in the public domain.
In the second review article, the authors examined how modern-day regulatory systems at the international level can create a barrier to access
to traditional herbal medicines. Regulatory mechanisms are intended to protect consumers by ensuring that consumers receive safe, efficacious,
and high-quality products. However, in the case of many herbal medicines, there are unintended consequences, so that in some cases, regulations
may create conditions that limit opportunities for the use of traditional herbal medicinal products. This is especially the case for herbal products
that are not widely recognized to have long-standing traditional uses in the global or national marketplaces. This review investigated and compared
how a Southern African herbal medicine (Mesembryanthemum tortuosum) with potential as an anxiolytic and mild antidepressant [12, 13]
has fared internationally in today’s regulatory environments. The authors argue that inadvertent regulatory favoritism combined with the inability
to secure associated intellectual property due to lack of means may create economic hurdles prohibiting successful product development and introduction
of botanicals from developing countries into most of the world’s health products markets.
In the third review article, the authors provide mechanistic and therapeutic insights into the neuroprotective effects of caffeic acid phenethyl
ester (CAPE) in CNS disorders .
Botanical sources of CAPE include the bark of conifer trees and propolis from beehives. Although relatively unexplored in human trials, CAPE
has been shown to have antioxidant, anti-inflammatory, antimitogenic, and anti-cancer activities in preclinical studies. It is thought to have the potential
for the treatment of neurological disorders through modulation of multiple molecular pathways and attenuation of behavioral deficits.
In the fourth review article, the authors summarize information of the phytochemistry, biological and cellular activities, and clinical trials of
several plant species to provide scientific baseline information that could be used in the drug development process to find drug leads for Alzheimer’s
disease (AD) and Parkinson’s disease (PD). AD and PD are complex, multifactorial age-associated diseases whose incidences are expected
to increase progressively with the increasing life expectancy worldwide. These two diseases cause suffering and pain of variable kinds
. Amyloid β peptide (Aβ)-induced toxicity is a well‐established pathway of neuronal cell death believed to play a vital role, in addition to
other events, in AD progression . When present in excess at the synapses, glutamate acts as a neurotoxin, causing excitotoxicity and contributing
to the pathogenesis of AD and PD . The few conventional drugs for the treatment of AD and PD have limited effectiveness and are
associated with adverse effects. This review examined botanicals that have been used for memory disorders in traditional medicine to evaluate
and determine the scientific basis, if any, for their reputed uses. The review presents a comprehensive look at plants and their constituents that
have shown promise in reversing: (i) amyloid-β -related toxicity in AD models; and (ii) glutamate-induced excitotoxicity in AD and PD models.
In the fifth review article, the authors present findings on Withania somnifera (L.) Dunal (WS), also known as ashwagandha. This medicinal
plant has commonly been used in Ayurvedic and other traditional Eastern medicine systems in many parts of the world [18, 19]. This review provides
a detailed, comprehensive summary of studies that examined the neuropsychiatric effects of WS for the management of stress, anxiety,
depression, and insomnia. The review found that WS root and leaf extracts exhibited noteworthy anti-stress and anxiolytic activities in both animal
and human clinical studies; positive effects were also found in the few studies that investigated its use for treating symptoms of depression
and insomnia. WS alleviated symptoms of these conditions predominately via modulation of the hypothalamic-pituitary-adrenal and sympatheticadrenal
medullary axes, as well as through the GABAergic and serotonergic pathways. Important observations were the significant variation in
the quality of WS extracts used in the studies reviewed and the lack of consensus on the best extraction method and dosage regimen for neuropsychiatric
applications. The authors recommended additional studies to elucidate the active constituents of WS. A few studies have demonstrated
that withanolide derivatives may be responsible for WS neuropsychiatric benefits; however, there is also evidence for the presence of additional,
and as of yet unidentified, active compounds [20-22]. Studies are also recommended to better design appropriate dosage regimens. Although WS
generally appears safe for human use, there is a need to investigate potential herb-drug interactions involving WS because of the likelihood to be
used concurrently with other medications as polypharmacy is common in aging adults .
In the final review article of this issue by Roe and Venkataraman, the authors examined the safety and efficacy of botanicals with nootropic
effects. The world’s population continues to live longer than ever before, and many people seek ways and means to keep healthy both physically
and mentally in their old age. In the wealthier developed countries, baby boomers are demanding products and services to help them stay youthful
both in mind and body and with the interest of “going” natural — plant-based products have become a major interest to help achieve this goal
. There is an increased demand for botanical dietary supplements with nootropic activities to help keep the mind active and sharp . Furthermore,
the authors examined data for various neuroactive botanicals targeted at improving cognitive function, stress reduction, and sleep. This
review article discusses acute and long-term clinical efficacy of data, current safety profiles of these botanicals, highlights data gaps for both efficacy
and safety and identifies future research needs.
Overall, the reviews in this special issue have provided an overview of some botanicals used traditionally for the treatment of neurological
disorders ranging from C. longa rhizome for epileptic seizures to W. somnifera for management of stress, anxiety, depression, and insomnia. An
important consideration is the overall lack of clinical studies to assess the claimed effects of these botanicals and very few animal toxicology studies.
Moreover, most of the few available studies were not properly designed. Furthermore, there is a lack of information on the quality of botanical
materials and extracts used; for example, in the case of WS, the authors state that there is a lack of consensus on the best extraction method
and dosage regimen for neuropsychiatric applications. Finally, the case of M. tortuosum highlights the barriers to entering the international health
product markets for lesser-known botanicals with therapeutic potential.
Future studies in this area could focus on well-designed clinical and toxicological studies to amass good quality data that would clarify the potential
of these botanicals to provide new treatments for neurological disorders.
It is known that the pain occurs with different intensities depending on the pathology and the area where the damage occurs.
The pain mechanisms involve different biochemical pathways and neurophysiological integration processes that are carried out
in the nervous system and finally, the cerebral cortex. Derived from the fact that pain is the main cause of medical care and can
be a cause of disability, in addition to the severity that occurs with the evolution of pathology such as bone tumors, there is a
greater impact on the patient with pain, aggravating the symptoms, reflecting a greater effect of the disease on the patient. All
these conditions generate a great negative impact on social and personal interrelationships, which leads to a great physiological
and emotional affectation that has a serious impact on the patient, as well as a growing desertion of work that leads to a high
In recent years, the number of patients with bone tumors and development of metastasis 60 to 85% of bone cancer patients
have been increased, where the main symptom is pain . In order to find new options to improve established treatments,
Romero-Morelos and collaborators set out a broader neurysiological approach, analyzing the processes of inflammation,
neuropathies and cognitive components to propose a new therapeutic approach that provides us with relevant information on
the relationship of these processes that have been managed in isolation and not as a dynamic component that encompasses a
single pathological process, so this work sought to identify the neurophysiology of mechanisms related to pain management in
bone tumors .
Because the relationship of inflammatory processes with the development of bone metastases is not well established, it is of
great importance to investigate the action of neurochemicals derived from inflammatory and tumor cells, while clarifying the
function of peripheral sensitization caused by nerve compression and injury caused by tumor growth . Based on the role
played by different neurochemical substances, the authors propose that the bone tumor can cause neuropathic and inflammatory
pain depending on the area where it is present and can affect both the peripheral nervous system as well as induce
neurochemical changes at the neurological level . The importance of pharmacological and non-pharmacological management
can be inferred from the information provided by the authors according to the system involved.
On the other hand, trigeminal neuralgia is characterized mainly by chronic pain in the trigeminal nerve, affecting the face
and brain, causing sudden unbearable pain. This condition is increasing and presents with an incidence of 2-13 per 100000
inhabitants per year and increases to 25 per 100,000 per year in people over 70 years of age , it is vitally important to address
treatments that help reduce the painful process, so various treatments have been proposed to reduce pain. Garcia-Isidoro and
collaborators performed a scientific evidence-based meta-analysis with the aim of evaluating the effectiveness of invasive and
non-invasive electrical neuromodulation of trigeminal neuralgia, on pain and adverse effects. These articles have been searched
and selected from the databases. In order to provide a new vision on the techniques used, the authors found that better results
have been obtained using short- and medium-term continuous radiofrequency, although pulsed radiofrequency showed a
smaller number of side effects after treatment, in addition to better results in the long term . One of the main problems was
performing the analysis, as the data were very heterogeneous, and no significant differences were found. However, what is
shown in this study provides certain information regading the techniques to be used by clinicians .
Finally, Pérez-Neri and colleagues analyzed the therapeutic potential of low-intensity, high-intensity focused ultrasound
neuromodulation for the management of neuropathic pain, which is especially useful in a group of chronic pain syndromes with
a restricted response to conventional drugs . The information presented is relevant, as it shows that low-intensity focused
ultrasound may modify some mechanisms involved in neuropathic pain processes such as modulation of ion channels,
glutamatergic neurotransmission, cerebral blood flow, inflammation and neurotoxicity, neuronal morphology and survival,
nerve regeneration and remyelination, as well as minor side effects . The authors propose that more clinical trials on safety
and efficacy are needed, despite the evidence provided on the potential therapeutic use of low-intensity, high-intensity focused
ultrasound for the management of neuropathic pain.
The information presented in this edition of Current Neuropharmacology provides an overview of current pain management
as a fundamental aspect of clinical practice, treatment, therapy and research. The contribution offered is of high academic level
that results in an interest of biomedical and clinical neurophasic and neuroscientists who work in research centers, hospitals, as
well as in the industry, since it can provide new therapeutic strategies for the treatment and reduction of pain on the patient, to
improve their quality of life.
Nowadays, many compounds have been discovered from natural origins. They are available either in nature or formulated
by the pharmaceutical industries for their multiple therapeutic properties. These natural compounds have been employed in
better management of various pathological conditions of the Central Nervous System (CNS). Some alternative surgeries have
been proposed for Parkinson´s disease (PD). These surgeries may require the control drug administration to the brain or
electrical implants to minimize involuntary muscular spasms [1, 2]. Thereby, both these approaches are not considered ideal
reliable alternatives to PD patients. Alzheimer´s disease (AD) is a chronic progressive neurodegenerative disorder wherein
memory loss slowly worsens over time [3, 4]. In the early stages of AD, memory impairment is modest. However, late-stage
Alzheimer's dementia symptoms are so severe that the patients lose their ability to perform basic care tasks .
Currently, chiral compounds and the complex heterocycles and hydrocarbon-cycles originated from marine and natural
compounds have been prepared by synthetic procedures. Molecular modeling simulation with respect to interactions within and
between common crystallized biological receptors has been widely explored. They were aimed to obtain computationally
designed medicines with ideal biological activity in explicit mental disorders.
Notably, the isolated natural alkaloids from marine and terrestrial resources have structural complexity. This results from
the living organisms’ requirements from their surroundings, the unpredictable pharmacological implementation of these
compounds at visceral and cutaneous level, and the chemical properties of these products depending on the nitrogen atoms
incorporated to feasible extensions of the aromatic system.
In the present special issue under the topic: "Parkinson´s and Alzheimer´s Diseases and Natural Products: Pathologies and
Medication of the New Times”, we have collected the scientific contributions in the field of neurochemistry in search of novel
therapeutic applications in treating Parkinson´s and Alzheimer´s disease. We employed designed heterocyclic and cyclic
hydrocarbon compositions originated from natural resources. Therefore, we included pharmacological-clinical trials, studies
with the content of synthesis and isolation, as well as theoretical investigations focusing on the structure-activity relationship in
This special issue contains 3 mini-review and full-review articles. We provided suitable figures, flow charts or tables for a
better understanding of the contents, whenever feasible. The first article presented in this special issue illustrated the summary
of symptoms affecting an individual's cognition state. Since dementia is severely debilitating, attempts to perceive an efficient
treatment for this condition is crucial. In this article, the authors attributed the demonstrated consequences of polydatin from a
In the second article, Tewari et al. described the reactive nitrogen species (RNS) and reactive oxygen species (ROS), well
known as reactive oxygen and nitrogen species (RONS), as the products of normal cellular metabolism. They stated that RONS
can interact with various vital biological molecules including nucleic acid, proteins, and membrane lipids.
Thereafter, the authors showed the critical role of nitric oxide (NO) for normal function of the human body. They also
attributed the significance of different natural products in various neurodegenerative diseases to their inhibitory effects on NO
production from the mechanistic perspective.
In the end, the last article in this issue by Singh et al. demonstrated that AD is the consequence of a multidirectional
pathology in the brain. They concluded that based on the AD pathophysiology, a multi-target-directed ligand (MTDL) strategy
This affirmation is the key for development and repurposing new agents for better management of AD with pyrimidine
based natural products. This biomolecule plays its role as a lead. In this review, the authors provided a list of herbal chemical
compounds to heal AD and alleviate its bothersome symptoms. Furthermore, they employed the active scaffolds of
pyrimidine/fused pyrimidines to protect against different potential targets of AD.
Cerebrovascular diseases are one of the leading causes of death and adult disability worldwide and most common types of
this diseases are ischemic stroke and hemorrhagic stroke. Blood-brain barrier (BBB) plays a vital role in regulating the
trafficking of fluid, solutes and cells at the blood-brain interface and maintaining the homeostatic microenvironment of the
central nervous system. Disruption of BBB has been proved closely related to the development of brain edema and neuronal
cell death in cerebrovascular diseases. Recently, major efforts have been made to investigate the pathological mechanisms of
BBB dysfunction, and develop pharmacological agents which would be able maintain BBB function after pathological events.
In this Special Issue on BBB dysfunction in Current Neuropharmacology, the authors provide the latest review on cellular and
molecular basis of BBB dysfunction, bring new insights into BBB protection, and point toward potential translation of
preclinical studies to improve the treatment of cerebrovascular diseases.
In this special issue, Okada and colleagues presented a panoramic view of current studies on BBB dysfunctions after
cerebrovascular diseases, including structure and function of BBB, techniques utilized to study BBB breakdown, biomarkers
and imaging techniques in clinical settings, as well as pathological mechanisms and therapeutic targets . They illustrated that
phenotypic transformation of myeloid cells such as macrophages and microglia regulates the initiation, evolution, and
resolution of inflammation, which compromise the integrity of BBB. Another group, Kang et al presented an in-depth
discussion on the diversity of microglia phenotypic polarizations and the communication between microglia and endothelial
cells after stroke. They concluded that the time pattern of microglia polarization may determine the therapeutic effect of
pharmacological agents . The crosstalk between inflammation and BBB dysfunction was eloquently elucidated by Ziping
Han’s team . They reviewed how the dynamic and bidirectional crosstalk between inflammation and BBB during stroke
occurs, and proposed personalized medicine for the treatment of stroke. The contribution from Shen and Ma represent an
important advance in the role of miRNAs in the modulation of BBB functions after ischemic stroke and highlight the role of
several miRNAs which are implicated in the pathogenesis of neonatal hypoxic-ischemic brain injury . As there is a
significant physiological difference between the developing and mature brain, more studies are needed to further determine the
protective effect of miRNAs in hypoxic-ischemic brain injury in neonates.
In subarachnoid hemorrhage (SAH) patients, BBB disruption is a critical contributor to the development of early brain
injury . The disruption is highly associated with increased mortality and poor prognosis. Li and colleagues summarized the
molecular mechanisms of BBB disruption after SAH, and stated that the apoptosis of endothelial cells and loss of tight junction
proteins are the two major causes responsible for BBB broken after SAH . They suggested, therefore, therapeutic strategies
against these two factors should be further explored in the future. Furthermore, Chen et al. addressed the recent clinical trials on
neuroprotection of SAH patients, including pharmacological and non- pharmacological approaches . The authors indicated
that intraventricular nimodipine shows the exciting result to achieve better clinical efficacy and fewer side effects. They also
considered that imaging techniques are promising tools to detect the abnormality of BBB and to predict the outcome in clinical
Angiogenesis is an important defense mechanism for the restoration of blood supply and re-organization of the neuronal
circuit following ischemic stroke . However, there is compelling concern that the therapeutic angiogenesis in vascular
remodeling after stroke accompanied with abnormally increased BBB permeability. Yang and Torbey presented an elegant
work in which they demonstrated that the abnormally high BBB permeability in peri-infarct areas is caused by a lack of major
tight junction proteins in endothelial cells in newly build vessels, and pericytes play a key role in tight junction formation
during angiogenesis . They recommended defining and optimizing restorative therapies by characterizing the cellular and
molecular mechanisms to facilitate functional BBB restoration without exacerbating brain edema and inflammation during
treatment of ischemic stroke. Given the prosperity of stem cell therapy in recent years, Gao et al. extensively illustrated the
effects and underlying mechanisms of cell therapy on the BBB permeability in ischemic stroke . There is still a great gap
between preclinical and clinical applications of stem cells, and some teething problems such as safety and ethical concerns need
to be ironed out.
Collectively, this Special Issue highlights several issues that are at the forefront of the BBB dysfunction in cerebral diseases.
A better understanding of these mechanisms will contribute to the identification of therapeutic targets and promote the
translational research of BBB protection.
Obsessive-compulsive (OC) spectrum disorders are a group of psychiatric disorders new to the
DSM. They are mainly characterized by repetitive thoughts, anxiety, emotional distress, and compulsive
behaviours. The specific types of obsessions, anxiety symptoms, and compulsive behaviours vary according to
each disorder. The DSM-5 distinguishes five main OC spectrum disorders: obsessive-compulsive disorder
(OCD); body dysmorphic disorder (BDD); hoarding disorder; hair-pulling disorder (trichotillomania); and skinpicking disorder (excoriation). Although these disorders have some similarities regarding characteristics of
patients, symptom presentation, neurobiological correlates, and treatment response, they are clearly distinct from
one another. This special issue aims to explore the rationale and the clinical practice of current pharmacological
strategies as related to the specific neurobiology of each OC spectrum disorder.
Addiction Medicine: What's new in this area?
The decline in both antioxidants and aging per se are associated with an increased risk of cognitive impairment, chronic
brain damage, the outcome of which can manifest as neurodegeneration. Based on recent reports, neurodegenerative diseases
affect more than 100 million people worldwide and cause significant economical and personal stress, and require long-term cost
effective care. The main motives and the key driving force in the field of neurodegenerative research, are the desire for solutions
to the ravages of CNS diseases especially, Alzheimer’s, Parkinson’s (respectively AD and PD), and others. An important
topic to address is the use of neuropharmacological-driven approaches that could attenuate neuroinflammatory processes in the
diseased brain, and improve the outcome. In this special issue of Current Neuropharmacology, contributors discuss a variety of
experimental and clinical approaches including the development and delivery of novel central nervous system agents, gene
therapies, and drug- and cell-based strategies, as well as micro RNA therapeutics. All of the treatments target CNS cellular
compartment mechanisms and/or the mediators leading to neurodegenerative diseases in vivo and/or cytotoxicity in vitro as
well. These downstream mechanisms include the activation of pro and/or anti-inflammatory signaling cascades, production of
oxygen, nitric oxide (including nitric oxide oxidation products such as nitrite and nitrate contain reactive species), excitatory
mediators and amino acids, and downregulation of growth factors that may lead to the development of neuronal injuries. Thus,
this special issue focuses on up-to-date research, targeting these pathways and mediators upon CNS damage and potential drug
Pouran Makhdoumi and coworkers report the molecular mechanism of aniline induced spleen and neuronal toxicity in
experimental rat exposure. It has been reported that the aniline exposure leads to neuron and spleen toxicity specifically, and
results in diverse neurological effects and sarcoma that are defined by splenomegaly, hyperplasia, and fibrosis and tumors’
formation at the end. However, the molecular mechanism(s) of aniline-induced spleen toxicity is not fully understood, and previous
studies have represented that aniline exposure results in iron overload and initiation of oxidative/nitrosative disorder
stress and oxidative damage to proteins, lipids and DNA, and subsequently, in the spleen. Elevated expression of cyclins, cyclin-
dependent kinases (CDKs) and phosphorylation of pRB protein along with increases in A, B and CDK1 as cell cycle regulatory
proteins cyclins, and reduction in CDK inhibitors (p21 and p27) could be critical in cell cycle regulation, which contribute
to tumorigenic response after aniline exposure. Critical analysis of the literature has shown that the aniline-induced splenic
toxicity is correlated to oxidative DNA damage and initiation of DNA glycosylases expression (OGG1, NEIL1/2, NTH1, APE1
and PNK) for removal of oxidative DNA lesions in the rat. Oxidative stress causes transcriptional up-regulation of fibrogenic/
inflammatory factors (cytokines, IL-1, IL-6 and TNF-α) via induction of nuclear factor-kappa B, AP-1 and redoxsensitive
transcription factors, in aniline treated-rats. The upstream signaling events as phosphorylation of IκB kinases (IKKα
and IKKβ) and mitogen-activated protein kinases (MAPKs) could potentially be the causes of activation of NF-κB and AP-1.
All of these events could initiate a fibrogenic and/or tumorigenic response in the spleen. Based on the authors’ interpretation,
most likely, the spleen toxicity of aniline has been studied more, and the different mechanisms are suggested. This review
summarizes those events following aniline exposure that induces spleen toxicity and neurotoxicity.
Muneeb U Rehman and coworkers report recent literature evidence regarding the implication of natural products as neuroprotective
strategies for neurological disorders. It has been well documented and reported that natural products can have a
significant role in the prevention of diseases and in boosting the health of humans and animals. These natural products have
been experimentally documented to possess various biological properties such as antioxidant, anti-inflammatory and antiapoptotic
activities. In vitro and in vivo studies have further established the usefulness of natural products in various preclinical
models of neurodegenerative disorders. Natural products include phytoconstituents, like polyphenolic antioxidants, found in
herbs, fruits, nuts, vegetables and also in marine and fresh water flora. These phytoconstituents may potentially suppress neurodegeneration
and improve memory as well as cognitive functions of the brain. Also, they are known to play a pivotal role in
the prevention and cure of different neurodegenerative diseases, such as AD, epilepsy, PD etc. The large scale neuropharmacological
activities of natural products have been documented which are due to the result of either inhibition of inflammatory
processes, and/or the up-regulation of various cell survival proteins and/or combination of both. Due to the scarcity of
human studies on neuroprotective effects of natural products, this review focuses on the various established activities of natural
products in in vitro and in vivo preclinical models, and their potential neurotherapeutic applications using the available knowledge
in the literature.
Studies by Faheem Hyder Pottoo and coworkers discussed the mechanisms of estrogen and serotonin: the complexity of
interactions and potential implications for epileptic seizures and epileptogenesis. Based on this report, burgeoning literature
documents the confluence of ovarian steroids and central serotonergic systems in the injunction of epileptic seizures and epileptogenesis.
In addition, estrogen administration in animals reduces neuronal death from seizures by up-regulation of the prosurvival
molecule i.e. Bcl-2, anti-oxidant potential and protection of NPY interneurons. Serotonin modulates epileptiform activity
in either direction i.e. by administration of 5-HT agonists or by reuptake of inhibitors that leads to the activation of 5-HT3 and
5-HT1A receptors tending to impede focal and generalized seizures, while depletion of brain 5-HT along with the destruction of serotonergic terminals leads to expanded neuronal excitability hence abatement of seizure threshold in experimental animal
models. Serotonergic neurotransmission is influenced by the organizational activity of steroid hormones in the growing brain
and the actuation effects of steroids which appear in adulthood. It is further established that ovarian steroids bring induction of
dendritic spine proliferation on serotonin neurons thus thawing a profound effect on serotonergic transmission. This review
features 5-HT1A and 5-HT3 receptors as potential targets for ameliorating seizure-induced neurodegeneration and recurrent
hypersynchronous neuronal activity. Indeed 5-HT3 receptors mediate a cross-talk between estrogenic and serotonergic pathways,
and could well be exploited for combinatorial drug therapy against epileptogenesis.
Ylia A. Sidorova and coworkers report the pathophysiology of PD and potential implication of small molecules as a new
treatment option for PD. PD is the second most common neurodegenerative disorder worldwide, the lifetime risk of developing
this disease is 1.5%. Motor diagnostic symptoms of PD are caused by degeneration of nigrostriatal dopamine neurons. Unfortunately,
there is no effective long-term treatment for PD and current therapy is limited to supportive care that partially alleviates
disease signs and symptoms. As diagnostic symptoms of PD result from progressive degeneration of dopaminergic neurons,
drugs restoring these neurons may significantly improve the treatment of PD. A literature search performed by Ylia A. Sidorova
et al., using the PubMed, Web of Science and Scopus databases discussed the progress achieved in the development of neurodegenerative
agents for PD. Based on this study, there are several groups of potential agents capable of protecting and restoring
dopamine neurons in vitro cell cultures as well as animal models that mimic PD including neurotrophic factors and small
molecular weight compounds. Based on the very careful analysis, authors’ conclusion is that in the promising results of in vitro
and in vivo experiments, none of the found agents have yet shown conclusive neurorestorative properties in PD patients.
Meanwhile, a few promising biological and small molecules have been identified. Their further clinical development could
eventually give rise to disease-modifying drugs for PD.
Dr. Iván Carrera and Professor Ramon Cacabelos present a report which demonstrates the current drugs and potential
future neuroprotective compounds in the context of PD. Unfortunately, the progress made so far in understanding the etiology
and pathogenesis of PD has only achieved the development of some clinical approaches intended to treat cognitive and behavioral
symptoms such as memory and perception disorders. Despite the major advances in different genetic causes and risk factors
for PD, which share common pathways to cell dysfunction and death, there is no complete model of PD that can be used to
accurately predict the effect of drugs on disease progression. In addition, clinical trials are also important to test any novel neuroprotective
agent, and recently, there have been great advances in the use of anti-inflammatory drugs and plant flavonoid antioxidants
to protect against specific neuronal degeneration and interference with lipid and cholesterol metabolism. The increasing
knowledge of the molecular events underlying the degenerative process of PD has stimulated research to identify natural
compounds capable of halting or slowing down the progress of neural deterioration. Polyphenols and flavonoids, which play a
neuroprotective role in a wide array of in vitro and in vivo models of neurological disorders, emerged from the multi-target bioagents
found mainly in plants and microorganisms. This review presents a detailed overview of the multimodal activities of
neuroprotective bio-agents tested so far, emphasizing their neurorescue/neuroregenerative activity. The brain-penetrating property
of bio-agents may make these compounds an important class of natural drugs for the treatment of neurodegenerative diseases.
Although there are numerous studies demonstrating beneficial effects in the laboratory by identifying critical molecular
targets, the clinical efficacy of these neuroprotective treatments remains to be proven accurately.
Mahmood Ahmad Khan and co-authors analyzed the current progress of peroxisome proliferator-activated receptor
gamma agonist as an emerging therapeutic approach for the treatment of AD. Peroxisome proliferator-activated receptors
(PPARs) are ligand-activated transcription factors known to play an important role in the regulation of glucose absorption, homeostasis
of lipid metabolism and are further involved in repressing the expression of genes related to inflammation. Thus,
agonists of this receptor represent an attractive therapeutic target for AD. In recent, both clinical and preclinical studies show
that using Peroxisome proliferator-activated receptor gamma (PPARγ) agonist improves both learning and memory along with
other AD-related pathologies. Thus , PPARγ signifies a significant new therapeutic target in treating AD. This review has shed
some light on the recent progress of how PPARγ agonist selectively modulates different cellular targets in AD and its potential
in the future treatment of AD.
Professor Gjumrakch Aliev’s research team critically analyzed the potential implication of dendrimer-based therapy for
AD. AD is characterized by the loss of neurons in different brain regions. It is the most common cause of dementia in the elderly
population accompanied by pathological degeneration of the neurons and formation of neurofibrillary tangles (NFT). Senile
plaques are formed with amyloid-beta (Aβ), hyperphosphorylated tau protein, apolipoprotein E and presenilin associated
with protease activity [Aβ, gamma-secretase (γS)]. The molecular mechanisms of neurodegeneration most likely include but are
not limited to apoptosis, oxidative stress (free radical generation that follows the cellular and subcellular damage), inflammation,
immune activation etc. The lack of effective treatments for AD stems mainly from the incomplete understanding of the
causes of AD. Currently, there are several hypotheses explaining the early mechanisms of AD pathogenesis. Recent years witnessed
an unprecedented research growth in the area of nanotechnology, which uses atomic, molecular and macromolecular
methods to create products in microscale (nanoscale) dimensions. This review article has discussed the role of nanotechnology
in the development and improvement of techniques for early diagnosis and effective treatment of AD. Moreover, since AD pathology
is practically irreversible, applications of disease-modifying treatments could be successful only if early diagnosis of AD is available. This review first time highlights various possibilities for the early diagnosis and therapy of AD, and investigates
potential adaptation of nanoparticles-dendrimers, a class of well-defined branched polymers, chemically synthesized with
a well-defined shape, size and nanoscopic physicochemical properties reminiscent of the proteins for the treatment of neurodegenerative
diseases including AD, PD and many others.
I am confident that review articles which are included in this special issue provide not only novel ideas to the pathophysiological
hallmarks of the different cellular compartments of the brain in the course of neurodegeneration, but also provide new
research directions regarding the treatment of CNS disorders in general.
Major advances in our understanding of the neurology/pathology, anatomy/physiology, and molecular biology
of the cerebellum have opened a new door for cerebellar ataxias (CAs). We have now entered in the ‘era of therapies’.
Cures are knocking at the door. We discuss the hot topics in the therapeutic protocols available for CAs, including aminopyridines,
noninvasive cerebellar stimulation, anti-oxidant drugs and therapies for immune-mediated cerbellar ataxias
(IMCAs), topics emphasized in this issue. The history of the cerebellum is a typical example of the importance of apparently
divergent and multi-disciplinary approaches.
Programmed cell death (PCD), referring to apoptosis, autophagy and programmed necrosis
(necroptosis and pyroptosis), plays crucial roles in the pathophysiology of stroke and has always
been the potential therapeutic target. Deciphering PCD signaling pathways helps to
understanding the molecular mechanisms of the brain disorders and promotes discovery of novel
therapeutic targets for stroke treatment.
The aims of this thematic issue are to review the progress of PCD signaling pathways in stroke,
and update the new advance of novel pharmacological and molecular treatment strategies
targeting PCD in the basic science research of stroke, translation and neurobiology of clinical
Eating disorders (anorexia nervosa, bulimia nervosa, binge eating disorder, and related
syndromes) are highly distinctive psychiatric disorders. The peak age of onset is 15–25 years,
a developmentally sensitive time. The average illness duration is about 6 years. Young
women make up the majority of people with anorexia and bulimia nervosa, with binge eating
disorder nearly equally common in both sexes. The prevalence of eating disorder behaviours
is rising in high-income countries, especially in combination with obesity. One in every six or
seven young women has an eating disorder and anorexia nervosa is one of the most common
chronic disorders in adolescence. Mortality rates are almost twice as high for people with
eating disorders as in the general population, and nearly six times higher for people with
anorexia nervosa. To date there is a lack in basic, neurobiologically informed research in
eating disorders. Alongside genetic research, brain imaging might help to elucidate
mechanisms related to brain pathophysiology that drive eating disorder behaviours. There are
also various endocrine alterations in eating disorders, and especially when patients are
underweight. However, such endocrine alterations frequently normalize with weight
restoration, and whether they specifically affect the brains and behaviours of patients with an
eating disorder is uncertain. Thus far pharmacotherapy has a secondary role in the treatment
of eating disorders and should not be considered as a sole or primary intervention
With this special issue on “Psychobiology of eating disorders” leading experts in the field of
eating disorders aim to provide current and up-to-date knowledge with focused and cutting
edge reviews of hot topics in eating disorders research to close the gap of bench to bedside
and facilitate a more individualized and precision medicine therapy approach in the treatment
of eating disorders for the future.
This hot topic issue reviews the most up to date literature dealing with pathophysiology
mechanisms underlying RGC death with the scope to propose new venues for the discovery of better
therapeutics on a rational basis.
Neurodegenerative diseases include Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS),
Parkinson's disease (PD), and Huntington's disease. These diseases involve different aspects of reward
processing (primary rewards, secondary rewards, reward-based learning, and reward-based decisionmaking).
About 70% of the population with 65 years or more are affected by these progressive
neurodegenerative disorders of the central nervous system and characterized by gradual loss of cognitive
function, progressive memory loss, disorientation, language impairment, abnormal behavior, personality
changes, etc Theoretical studies using in silico methods have aided in the process of drug discovery.
Technological advances in the areas of structural characterization, computational science, and molecular
biology have contributed to faster planning of new feasible molecules. Chemoinformatic studies show
that a large fraction of compoundss are “drug-like” or at least, “lead-like” having structural and
physicochemical properties that render them as potential drugs or leads. This thematic issue will bring
together theoretical studies of different methodologies, such as QSAR, docking, chemometric tools,
artificial intelligence and other applied in order to optimize the search for new drugs for the cure and
treatment of neurodegenerative diseases.
Traditionally, neuroscientists regarded glial functions as simply providing physical support
and maintenance for neurons. Thus, in this limited role glia had been long ignored. Recently,
glial functions have been gradually investigated, and increasing evidence has suggested that glial
cells perform important roles in various brain functions. Digging up the glial functions and
further understanding of these crucial cells, and the interaction between neurons and glia may
shed new light on clarifying many unknown aspects including the mind-brain gap, and
conscious-unconscious relationships. It is well known that CNS inflammation and immune
activation play a major role in the pathophysiology of neurodegenerative diseases. Although the
blood-brain barrier is able to protect the CNS from immune activation, it becomes more
permeable during inflammation, which renders the brain vulnerable to infections. A better
understanding of the interaction between inflammatory mediators, such as cytokines, and the
activated immune response, including astrocytes and microglia, is critical for the development of
new therapeutic strategies for neurodegenerative diseases.
The goal of this SI is to review the relationship of neuron-glia and cytokines in the
pathophysiology of neuropsychiatric disorders and the mechanisms of action of drugs used for
their treatment. The SI provides evidences for the role of the inflammation induced toxic
metabolites from the tryptophan pathway in neuropsychiatric disorders such as depression,
schizophrenia, and Alzheimer's disease and so on. A better understanding of the interaction
between cytokines, glia and neurons provide new strategies for the development of novel
therapeutic targets for neuropsychiatric disorders.
This themed issue aims to bring together recent findings in basic and clinical sciences with a
translational perspective that will cover the involvement of the nicotinic cholinergic system not only in
physiological functions but also in disease states, including but not limited to tobacco addiction, as well
as drug development.
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