Abstract
Lewy bodies (LBs) and Lewy neurites (LNs) in the brain constitute the main histopathological features of Parkinsons disease (PD) and dementia with Lewy bodies (DLB), and are comprised of amyloid-like fibrils composed of a small protein (∼14 kDa) named alpha-synuclein (αS). As the aggregation of αS in the brain has been implicated as a critical step in the development of the diseases, the current search for disease-modifying drugs is focused on modification of the process of αS deposition in the brain. In this article, the recent developments on the molecules that inhibit the formation of α-synuclein fibrils (fαS) as well as the oligomerization of αS are reviewed. Recently, various compounds such as curcumin, nicotine and wine-related polyphenols have been reported to inhibit the formation of fαS, and to destabilize preformed fαS at pH 7.5 at 37°C in vitro. Although the mechanisms by which these compounds inhibit fαS formation from fαS, and destabilize preformed fαS are still unclear, they could be key molecules for the development of preventives and therapeutics for PD and other α-synucleinopathies.
Keywords: Parkinson's disease, α-synuclein fibrils, oligomer, organic compounds, thioflavin S, electron microscopy, atomic force microscopy
Current Pharmaceutical Design
Title: β-Synuclein Assembly as a Therapeutic Target of Parkinsons Disease and Related Disorders
Volume: 14 Issue: 30
Author(s): Kenjiro Ono, Mie Hirohata and Masahito Yamada
Affiliation:
Keywords: Parkinson's disease, α-synuclein fibrils, oligomer, organic compounds, thioflavin S, electron microscopy, atomic force microscopy
Abstract: Lewy bodies (LBs) and Lewy neurites (LNs) in the brain constitute the main histopathological features of Parkinsons disease (PD) and dementia with Lewy bodies (DLB), and are comprised of amyloid-like fibrils composed of a small protein (∼14 kDa) named alpha-synuclein (αS). As the aggregation of αS in the brain has been implicated as a critical step in the development of the diseases, the current search for disease-modifying drugs is focused on modification of the process of αS deposition in the brain. In this article, the recent developments on the molecules that inhibit the formation of α-synuclein fibrils (fαS) as well as the oligomerization of αS are reviewed. Recently, various compounds such as curcumin, nicotine and wine-related polyphenols have been reported to inhibit the formation of fαS, and to destabilize preformed fαS at pH 7.5 at 37°C in vitro. Although the mechanisms by which these compounds inhibit fαS formation from fαS, and destabilize preformed fαS are still unclear, they could be key molecules for the development of preventives and therapeutics for PD and other α-synucleinopathies.
Export Options
About this article
Cite this article as:
Ono Kenjiro, Hirohata Mie and Yamada Masahito, β-Synuclein Assembly as a Therapeutic Target of Parkinsons Disease and Related Disorders, Current Pharmaceutical Design 2008; 14 (30) . https://dx.doi.org/10.2174/138161208786404191
DOI https://dx.doi.org/10.2174/138161208786404191 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Effect of S-equol and Soy Isoflavones on Heart and Brain
Current Cardiology Reviews Brain Aging in African-Americans: The Atherosclerosis Risk in Communities (ARIC) Experience
Current Alzheimer Research Selective Acetyl- and Butyrylcholinesterase Inhibitors Reduce Amyloid-β Ex Vivo Activation of Peripheral Chemo-cytokines From Alzheimer's Disease Subjects: Exploring the Cholinergic Anti-inflammatory Pathway
Current Alzheimer Research Exploration of Potent Multi-target-directed-ligands as Anti-alzheimer’s Disease Agents: A Moiety Based Review
Mini-Reviews in Medicinal Chemistry Dissecting the Biological Effects of Isoflurane through the Mechanistic Target of Rapamycin (mTOR) and microRNAs (miRNAs)
Current Neurovascular Research Phosphodiesterase Inhibitors as a Target for Cognition Enhancement in Aging and Alzheimer’s Disease: A Translational Overview
Current Pharmaceutical Design Inducible Nitric Oxide Synthase as a Possible Target in Hypertension
Current Drug Targets O-GlcNAc Modification and the Tauopathies: Insights from Chemical Biology
Current Alzheimer Research Prevalence and associated factors of sarcopenia in elderly subjects with amnestic mild cognitive impairment or Alzheimer disease.
Current Alzheimer Research The Potential Role of Sirtuins Regarding the Effects of Exercise on Aging- Related Diseases
Current Aging Science Structural Exploration of Synthetic Chromones as Selective MAO-B Inhibitors: A Mini Review
Combinatorial Chemistry & High Throughput Screening Imaging Epigenetics in Alzheimer’s Disease
Current Pharmaceutical Design <i>Nigella sativa</i> L., Supplementary Plant with Anticholinesterase Effect for Cognition Problems: A Kinetic Study
Current Aging Science Reviewing the Cardiovascular Complications of HIV Infection After the Introduction of Highly Active Antiretroviral Therapy
Current Drug Targets - Cardiovascular & Hematological Disorders Nutritional Antioxidants and Adaptive Cell Responses: An Update
Current Molecular Medicine Editorial (Hot Topic :Treatment with Antidepressants)
Current Pharmaceutical Design Crossed Cerebellar Diaschisis in Alzheimer’s Disease
Current Alzheimer Research Flow and Microwave Assisted Synthesis of Medicinally Relevant Indoles
Current Green Chemistry An Overview on Potential Neuroprotective Compounds for Management of Alzheimer’s Disease
CNS & Neurological Disorders - Drug Targets Targeting Beta-Amyloid Pathogenesis Through Acetylcholinesterase Inhibitors
Current Pharmaceutical Design