Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disease afflicting about 1% of people over 65 years old and 4-5% of people over 85 years. It is proposed that a cascade of deleterious factors is set in motion within that neuron made not of one, but rather of multiple factors such as free radicals, excitotoxicity, neuroinflammation, and apoptosis to cite only some of the most salient. In this scenario, chronic systemic inflammation, as well as impaired mitochondrial metabolism, have also been suspected of playing a role in the development of type-2 diabetes, and the possibility of a shared pathophysiology of PD and type-2 diabetes has been proposed. The discussion about the interactions between PD and type-2 diabetes mellitus began in the 1960’s and there is still controversy. Insulin and dopamine may exert reciprocal regulation hence; hypoinsulinemia induced by streptozotocin decreased the amounts of dopamine transporter and tyrosine hydroxylase transcripts in the substantia nigra pars compacta. Accordingly, dopamine depletion in the striatum is able to decreases insulin signaling in basal ganglia, indicating that, perhaps, PD may be considered as a risk factor for the development of type-2 diabetes mellitus. In this sense, it is described that peroxisome proliferator-activated receptor-γ, ATP-sensitive K+ channels, AMP-activated protein kinase, glucagon-like peptide-1 and dipeptidyl peptidase-4 are important therapeutic targets for PD and reinforces the association with diabetes. Therefore, the objective of the present review is to contextualize the mutual pathophysiological interactions between PD and type-2 diabetes mellitus, as well as the potential common treatments.
Keywords: Dopamine, Treatment, Peroxisome proliferator-activated receptor-γ, Type-2 diabetes mellitus, Parkinson´s disease.
CNS & Neurological Disorders - Drug Targets
Title:Does Parkinson’s Disease and Type-2 Diabetes Mellitus Present Common Pathophysiological Mechanisms and Treatments?
Volume: 13 Issue: 3
Author(s): Marcelo M.S. Lima, Adriano D.S. Targa, Ana C.D. Noseda, Lais S. Rodrigues, Ana Marcia Delattre, Fabiola V. dos Santos, Mariana H. Fortes, Maira J. Maturana and Anete C. Ferraz
Affiliation:
Keywords: Dopamine, Treatment, Peroxisome proliferator-activated receptor-γ, Type-2 diabetes mellitus, Parkinson´s disease.
Abstract: Parkinson’s disease (PD) is the second most common neurodegenerative disease afflicting about 1% of people over 65 years old and 4-5% of people over 85 years. It is proposed that a cascade of deleterious factors is set in motion within that neuron made not of one, but rather of multiple factors such as free radicals, excitotoxicity, neuroinflammation, and apoptosis to cite only some of the most salient. In this scenario, chronic systemic inflammation, as well as impaired mitochondrial metabolism, have also been suspected of playing a role in the development of type-2 diabetes, and the possibility of a shared pathophysiology of PD and type-2 diabetes has been proposed. The discussion about the interactions between PD and type-2 diabetes mellitus began in the 1960’s and there is still controversy. Insulin and dopamine may exert reciprocal regulation hence; hypoinsulinemia induced by streptozotocin decreased the amounts of dopamine transporter and tyrosine hydroxylase transcripts in the substantia nigra pars compacta. Accordingly, dopamine depletion in the striatum is able to decreases insulin signaling in basal ganglia, indicating that, perhaps, PD may be considered as a risk factor for the development of type-2 diabetes mellitus. In this sense, it is described that peroxisome proliferator-activated receptor-γ, ATP-sensitive K+ channels, AMP-activated protein kinase, glucagon-like peptide-1 and dipeptidyl peptidase-4 are important therapeutic targets for PD and reinforces the association with diabetes. Therefore, the objective of the present review is to contextualize the mutual pathophysiological interactions between PD and type-2 diabetes mellitus, as well as the potential common treatments.
Export Options
About this article
Cite this article as:
Lima M.S. Marcelo, Targa D.S. Adriano, Noseda C.D. Ana, Rodrigues S. Lais, Delattre Marcia Ana, Santos V. dos Fabiola, Fortes H. Mariana, Maturana J. Maira and Ferraz C. Anete, Does Parkinson’s Disease and Type-2 Diabetes Mellitus Present Common Pathophysiological Mechanisms and Treatments?, CNS & Neurological Disorders - Drug Targets 2014; 13 (3) . https://dx.doi.org/10.2174/18715273113126660155
DOI https://dx.doi.org/10.2174/18715273113126660155 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Atranorin – An Interesting Lichen Secondary Metabolite
Mini-Reviews in Medicinal Chemistry Amyloid-β Aggregation Inhibitory and Neuroprotective Effects of Xanthohumol and its Derivatives for Alzheimer’s Diseases
Current Alzheimer Research Quadruplex DNA: A Promising Drug Target for the Medicinal Inorganic Chemist
Current Topics in Medicinal Chemistry The Heat Shock Protein 90 Chaperone Complex: An Evolving Therapeutic Target
Current Cancer Drug Targets Bacterial Toxins: Potential Weapons Against HIV Infection
Current Pharmaceutical Design Tumor Control by Manipulation of the Human Anti-Apoptotic Survivin Gene
Current Cancer Therapy Reviews Polyphenols Beyond Barriers: A Glimpse into the Brain
Current Neuropharmacology “SLY AS A FOXO”: New Paths with Forkhead Signaling in the Brain
Current Neurovascular Research The Relationship Between Cleft Lip, Maxillary Hypoplasia, Hypoxia and Phenytoin
Current Pharmaceutical Design Significance of Genome-Wide Analysis of Copy Number Alterations and UPD in Myelodysplastic Syndromes using Combined CGH – SNP Arrays
Current Medicinal Chemistry The High Throughput Biomedicine Unit at the Institute for Molecular Medicine Finland: High Throughput Screening Meets Precision Medicine
Combinatorial Chemistry & High Throughput Screening The Epithelial-Mesenchymal Transition and Cancer Stem Cells: Functional and Mechanistic Links
Current Pharmaceutical Design Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Other Anti- Inflammatory Agents in the Treatment of Neurodegenerative Disease
Current Alzheimer Research Histone Deacetylases: Anti-Angiogenic Targets in Cancer Therapy
Current Cancer Drug Targets Genetic Chemoprotection with Mutant O6-Alkylguanine-DNA-Alkyltransferases
Current Gene Therapy Small Molecules Targeting p53 to Improve Antitumor Therapy
Mini-Reviews in Medicinal Chemistry Design of New Drug Molecules to be Used in Reversing Multidrug Resistance in Cancer Cells
Current Cancer Drug Targets A Comparative Analysis of Brain and Plasma Aβ Levels in Eight Common Non-Transgenic Mouse Strains: Validation of a Specific Immunoassay for Total Rodent Aβ
Current Alzheimer Research Autophagy as a Molecular Target of Flavonoids Underlying their Protective Effects in Human Disease
Current Medicinal Chemistry Antigenic Differences Between Normal and Malignant Cells as a Basis for Treatment of Intracerebral Neoplasms Using a DNA-Based Vaccine
Current Genomics