Abstract
Dementia with Lewy bodies (DLB), the second most frequent cause of dementia after Alzheimer disease (AD), is characterized by the widespread distribution of Lewy bodies in virtually every brain area. Clinically, DLB is distinguished from AD by fluctuating cognition, prominent visual hallucinations and parkinsonism, and from Parkinson disease, by the appearance of parkinsonism within one year of cognitive or behavioral decline. The main component of Lewy bodies is alpha-synuclein. Accumulating evidence suggests that its aggregation constitutes one of the first steps preceeding Lewy body formation, so that antiaggregation strategies would be very useful to prevent alpha-synuclein fibril formation. Main therapies nevertheless applied up to the present remain symptomatological. In this context, cholinesterase inhibitors such as rivastigmine, galantamine and donepezil, are used for the treatment of delusions and other psychotic symptoms. This review focuses on the recent discovery of possible alpha-synuclein anti-aggregation factors, where four main classes can be defined. First, beta-synuclein as well as alpha-synuclein derived peptides in addition to antibodies present a group of proteins and peptides that directly interact with alpha-synuclein and so inhibit its aggregation. Second, small molecules interfere with alpha-synuclein aggregation by their covalent binding, although not all of them are suitable for an appropriate inhibition of alpha-synuclein aggregation. Third, to inhibit the expression of alpha-synuclein and its isoforms at the RNA level, the use of interference RNA represents a future challenge. The fourth strategy is based on the enhancement of inclusion body formation to accelerate the elimination of soluble alpha-synuclein oligomers. Each chapter section includes the discussion of possible strategies for the development of drugs and therapies.
Keywords: Dementia, Alpha-Synuclein, Antiaggregatory, Alzheimer disease (AD), Parkinson disease, cholinesterase inhibitors, galantamine, psychotic symptoms, anti-aggregation factors
Current Medicinal Chemistry
Title: The Therapeutical Potential of Alpha-Synuclein Antiaggregatory Agents for Dementia with Lewy Bodies
Volume: 15 Issue: 26
Author(s): Katrin Beyer and Aurelio Ariza
Affiliation:
Keywords: Dementia, Alpha-Synuclein, Antiaggregatory, Alzheimer disease (AD), Parkinson disease, cholinesterase inhibitors, galantamine, psychotic symptoms, anti-aggregation factors
Abstract: Dementia with Lewy bodies (DLB), the second most frequent cause of dementia after Alzheimer disease (AD), is characterized by the widespread distribution of Lewy bodies in virtually every brain area. Clinically, DLB is distinguished from AD by fluctuating cognition, prominent visual hallucinations and parkinsonism, and from Parkinson disease, by the appearance of parkinsonism within one year of cognitive or behavioral decline. The main component of Lewy bodies is alpha-synuclein. Accumulating evidence suggests that its aggregation constitutes one of the first steps preceeding Lewy body formation, so that antiaggregation strategies would be very useful to prevent alpha-synuclein fibril formation. Main therapies nevertheless applied up to the present remain symptomatological. In this context, cholinesterase inhibitors such as rivastigmine, galantamine and donepezil, are used for the treatment of delusions and other psychotic symptoms. This review focuses on the recent discovery of possible alpha-synuclein anti-aggregation factors, where four main classes can be defined. First, beta-synuclein as well as alpha-synuclein derived peptides in addition to antibodies present a group of proteins and peptides that directly interact with alpha-synuclein and so inhibit its aggregation. Second, small molecules interfere with alpha-synuclein aggregation by their covalent binding, although not all of them are suitable for an appropriate inhibition of alpha-synuclein aggregation. Third, to inhibit the expression of alpha-synuclein and its isoforms at the RNA level, the use of interference RNA represents a future challenge. The fourth strategy is based on the enhancement of inclusion body formation to accelerate the elimination of soluble alpha-synuclein oligomers. Each chapter section includes the discussion of possible strategies for the development of drugs and therapies.
Export Options
About this article
Cite this article as:
Beyer Katrin and Ariza Aurelio, The Therapeutical Potential of Alpha-Synuclein Antiaggregatory Agents for Dementia with Lewy Bodies, Current Medicinal Chemistry 2008; 15 (26) . https://dx.doi.org/10.2174/092986708786242868
DOI https://dx.doi.org/10.2174/092986708786242868 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Subcutaneous Immunoglobulins: A Promising Alternative for Immunomodulation?
Current Pharmaceutical Design Potential Therapeutic Approaches to Alzheimer’s Disease By Bioinformatics, Cheminformatics And Predicted Adme-Tox Tools
Current Neuropharmacology Multiple Species Metabolism of PHA-568487, A Selective α7 Nicotinic Acetylcholine Receptor Agonist
Drug Metabolism Letters Predicting Progression from Cognitive Impairment to Alzheimer’s Disease with the Disease State Index
Current Alzheimer Research The LDL-Receptor and its Molecular Properties: From Theory to Novel Biochemical and Pharmacological Approaches in Reducing LDL-cholesterol
Current Medicinal Chemistry Vascular Risk Factors and Neurodegeneration in Ageing Related Dementias: Alzheimer’s Disease and Vascular Dementia
Current Alzheimer Research Structure – Function Relationships of Pre-Fibrillar Protein Assemblies in Alzheimers Disease and Related Disorders
Current Alzheimer Research Generic Clopidogrel Besylate in the Secondary Prevention of Atherothrombotic Events: A 6-month Follow-up of a Randomised Clinical Trial
Current Vascular Pharmacology The prediction of response to Galantamine treatment in Patients with mild to moderate Alzheimer’s Disease
Current Alzheimer Research Technological Solutions for Older People with Alzheimer’s Disease: Review
Current Alzheimer Research Pneumonia in the Elderly
Current Respiratory Medicine Reviews A Comparison Between Quetiapine and Aripiprazole for Treatment of Schizophrenia: A Double Blind Contrast
Current Psychopharmacology Insights Into Effects of Ellagic Acid on the Nervous System: A Mini Review
Current Pharmaceutical Design Global View on Alzheimer’s Disease and Diabetes Mellitus: Threats, Risks and Treatment Alzheimer’s Disease and Diabetes Mellitus
Current Alzheimer Research Autism: Pathophysiology and Promising Herbal Remedies
Current Pharmaceutical Design Defining Dystonic Tremor
Current Neuropharmacology Overactive Bladder - Current Treatment Modalities
Current Women`s Health Reviews 5-HT6 Receptor Antagonists as Potential Therapeutics for Cognitive Impairment
Current Topics in Medicinal Chemistry Fyn Kinase in Brain Diseases and Cancer: The Search for Inhibitors
Current Medicinal Chemistry β-Amyloid, Neuronal Death and Alzheimers Disease
Current Molecular Medicine