Abstract
Small molecule interactions with amyloid proteins have had a huge impact in Alzheimer's disease (AD), especially in three specific areas: amyloid folding, metabolism and brain imaging. Amyloid plaque amelioration or prevention have, until recently, driven drug development, and only a few drugs have been advanced for use in AD. Amyloid proteins undergo misfolding and oligomerization via intermediates, eventually forming protease resistant amyloid fibrils. These fibrils accumulate to form the hallmark amyloid plaques and tangles of AD. Amyloid binding compounds can be grouped into three categories, those that: i) prevent or reverse misfolding, ii) halt misfolding or trap intermediates, and iii) accelerate the formation of stable and inert amyloid fibrils. Such compounds include hydralazine, glycosaminoglycans, curcumin, beta sheet breakers, catecholamines, and ATP. The versatility of amyloid binding compounds suggests that the amyloid structure may serve as a scaffold for the future development of sensors to detect such compounds. Metabolic dysfunction is one of the earliest pathological features of AD. In fact, AD is often referred to as type 3 diabetes due to the presence of insulin resistance in the brain. A recent study indicates that altering metabolism improves cognitive function. While metabolic reprogramming is one therapeutic avenue for AD, it is more widely used in some cancer therapies. FDA approved drugs such as metformin, dichloroacetic acid (DCA), and methylene blue can alter metabolism. These drugs can therefore be potentially applied in alleviating metabolic dysfunction in AD. Brain imaging has made enormous strides over the past decade, offering a new window to the mind. Recently, there has been remarkable development of compounds that have the ability to image both types of pathological amyloids: tau and amyloid beta. We have focused on the low cost, simple to use, near infrared fluorescence (NIRF) imaging probes for amyloid beta (Aβ), with specific attention on recent developments to further improve contrast, specificity, and sensitivity. With advances in imaging technologies, such fluorescent imaging probes will open new diagnostic avenues.
Keywords: Alzheimer's disease, amyloid binding, animal models, ATP, brain imaging, near infrared fluorescence, small compounds.
Current Alzheimer Research
Title:Small Molecules and Alzheimer’s Disease: Misfolding, Metabolism and Imaging
Volume: 12 Issue: 5
Author(s): Shahrzad Abdollahi, Ian V.J. Murray, Tuula O. Jalonen, Chongzhao Ran, Janelle N. Fawver, Karen T. Duong, Nikhita Gadi, Rachel A. Gonnella, Stacey Charles, Viharkumar Patel, Pardeep S. Taunk, Hee Chang Sung, Melvin Baidya, Opeyemi O. Owa, Akwe N. Nyabera, Nicolas A. Tautiva and Xueli Zhang
Affiliation:
Keywords: Alzheimer's disease, amyloid binding, animal models, ATP, brain imaging, near infrared fluorescence, small compounds.
Abstract: Small molecule interactions with amyloid proteins have had a huge impact in Alzheimer's disease (AD), especially in three specific areas: amyloid folding, metabolism and brain imaging. Amyloid plaque amelioration or prevention have, until recently, driven drug development, and only a few drugs have been advanced for use in AD. Amyloid proteins undergo misfolding and oligomerization via intermediates, eventually forming protease resistant amyloid fibrils. These fibrils accumulate to form the hallmark amyloid plaques and tangles of AD. Amyloid binding compounds can be grouped into three categories, those that: i) prevent or reverse misfolding, ii) halt misfolding or trap intermediates, and iii) accelerate the formation of stable and inert amyloid fibrils. Such compounds include hydralazine, glycosaminoglycans, curcumin, beta sheet breakers, catecholamines, and ATP. The versatility of amyloid binding compounds suggests that the amyloid structure may serve as a scaffold for the future development of sensors to detect such compounds. Metabolic dysfunction is one of the earliest pathological features of AD. In fact, AD is often referred to as type 3 diabetes due to the presence of insulin resistance in the brain. A recent study indicates that altering metabolism improves cognitive function. While metabolic reprogramming is one therapeutic avenue for AD, it is more widely used in some cancer therapies. FDA approved drugs such as metformin, dichloroacetic acid (DCA), and methylene blue can alter metabolism. These drugs can therefore be potentially applied in alleviating metabolic dysfunction in AD. Brain imaging has made enormous strides over the past decade, offering a new window to the mind. Recently, there has been remarkable development of compounds that have the ability to image both types of pathological amyloids: tau and amyloid beta. We have focused on the low cost, simple to use, near infrared fluorescence (NIRF) imaging probes for amyloid beta (Aβ), with specific attention on recent developments to further improve contrast, specificity, and sensitivity. With advances in imaging technologies, such fluorescent imaging probes will open new diagnostic avenues.
Export Options
About this article
Cite this article as:
Abdollahi Shahrzad, Murray V.J. Ian, Jalonen O. Tuula, Ran Chongzhao, Fawver N. Janelle, Duong T. Karen, Gadi Nikhita, Gonnella A. Rachel, Charles Stacey, Patel Viharkumar, Taunk S. Pardeep, Sung Chang Hee, Baidya Melvin, Owa O. Opeyemi, Nyabera N. Akwe, Tautiva A. Nicolas and Zhang Xueli, Small Molecules and Alzheimer’s Disease: Misfolding, Metabolism and Imaging, Current Alzheimer Research 2015; 12 (5) . https://dx.doi.org/10.2174/1567205012666150504145646
DOI https://dx.doi.org/10.2174/1567205012666150504145646 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Early nutritional intervention and physical activity in the prevention of Alzheimer's disease and other dementias
The aim is to broaden the knowledge about the impact of the consumption of food ingredients, diet ingredients, methods of processing of food raw materials as well as the impact of composing of diets on the possibility of preventing Alzheimer's disease and other types of dementia at each stage of ...read more
Enhancing Alzheimer's Disease Diagnosis and Treatment Efficacy Prediction with Explainable AI, Radiomics, Biomarkers, and Multimodal Neuroimaging
The thematic issue, Enhancing Alzheimer's Disease Diagnosis and Treatment Efficacy Prediction with Explainable AI, Radiomics, Biomarkers, and Multimodal Neuroimaging, aims to bridge the gap between advanced computational techniques and clinical practice in Alzheimer’s disease research. Alzheimer’s disease poses significant challenges in early diagnosis, disease progression monitoring, and predicting treatment efficacy. ...read more
Integrative Perspectives on Neurodegeneration and Aging: From Molecular Insights to Therapeutic Strategies
The increasing burden of age-related neurodegenerative diseases demands an immediate and pressing need for research in all aspects, from molecular mechanisms to therapeutic interventions. The special issue in Current Alzheimer Research "Integrative Perspectives on Neurodegeneration and Aging: From Molecular Insights to Therapeutic Strategies" aims to highlight the summary of state-of-the-art ...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
- Announcements
Related Articles
-
Tumor Stroma Manipulation By MSC
Current Drug Targets An Overview on Different Classes of Viral Entry and Respiratory Syncitial Virus (RSV) Fusion Inhibitors
Current Medicinal Chemistry Protective Effects of Isothiocyanates against Alzheimer's Disease
Current Traditional Medicine Adhesion Molecules in Lung Cancer: Implications in the Pathogenesis and Management
Current Pharmaceutical Design Confomational Analysis of Soluble Oligomers of GFP Tagged Prion Protein By Fluorescence Fluctuation Spectroscopy
Current Pharmaceutical Biotechnology Inhibitory Activity of Curcumin Derivatives Towards Metal-Free and Metal-Induced Amyloid-β Aggregation
Current Alzheimer Research Moving Beyond Tyrosine Hydroxylase to Define Dopaminergic Neurons for Use in Cell Replacement Therapies for Parkinson’s Disease
CNS & Neurological Disorders - Drug Targets Anticancer Alkylphospholipids: Mechanisms of Action, Cellular Sensitivity and Resistance, and Clinical Prospects
Current Pharmaceutical Design MiR-340 Reduces the Accumulation of Amyloid-β Through Targeting BACE1 (β-site Amyloid Precursor Protein Cleaving Enzyme 1) in Alzheimer’s Disease
Current Neurovascular Research New Avenue of Research: Antiepileptic Drug and Estradiol Neuroprotection in Epilepsy
Recent Patents on CNS Drug Discovery (Discontinued) Anti-Inflammatory and Anti-Neoplastic Actions of Resveratrol
Current Nutrition & Food Science A Possible Modulation Mechanism of Intramolecular and Intermolecular Interactions for NCAM Polysialylation and Cell Migration
Current Topics in Medicinal Chemistry Ketamine as Antidepressant? Current State and Future Perspectives
Current Neuropharmacology Neurokinin Receptors and Subtypes as Potential Targets in Breast Cancer: Relevance to Bone Marrow Metastasis
Drug Design Reviews - Online (Discontinued) Cancer Immunotherapy: Battling Tumors with Gene Vaccines
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Targeting Myc in Pediatric Malignancies of the Central and Peripheral Nervous System
Current Cancer Drug Targets Opioid Receptor Interacting Proteins and the Control of Opioid Signaling
Current Pharmaceutical Design Real Time Analysis of Neurotransmitters in the Brain Using a Micro-Electrode System
Current Neurovascular Research Dissecting the Therapeutic Relevance of Gene Therapy in NeuroAIDS: An Evolving Epidemic
Current Gene Therapy Polymeric Carriers for Gene Delivery: Chitosan and Poly(amidoamine) Dendrimers
Current Pharmaceutical Design