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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
REM sleep and its Loss-Associated Epigenetic Regulation with Reference to Noradrenaline in Particular
Current Neuropharmacology The role of NADPH Oxidase in Vascular Disease – Hypertension, Atherosclerosis & Stroke
Current Pharmaceutical Design Postprandial Glucose - A Potential Therapeutic Target to Reduce Cardiovascular Mortality
Current Vascular Pharmacology Essential Fatty Acids - A Review
Current Pharmaceutical Biotechnology Role of Dietary Polyphenols in Attenuating Brain Edema and Cell Swelling in Cerebral Ischemia
Recent Patents on CNS Drug Discovery (Discontinued) CYP-Mediated Clozapine Interactions: How Predictable Are They?
Current Drug Metabolism State Dissociation, Human Behavior, and Consciousness
Current Topics in Medicinal Chemistry Statin Therapy-Evidence Beyond Lipid Lowering Contributing to Plaque Stability
Current Medicinal Chemistry VNTR Variant of the <i>eNOS</i> Gene and its Relationship with Osteoporosis in Postmenopausal Turkish Women
Endocrine, Metabolic & Immune Disorders - Drug Targets Androgen Therapy in Male Patients Suffering from Type 2 Diabetes: A Review of Benefits and Risks
Current Diabetes Reviews Calpain Inhibition: A Therapeutic Strategy Targeting Multiple Disease States
Current Pharmaceutical Design Central Nervous System-Related
Current Bioactive Compounds Functional and Structural Alterations of Large Arteries: Methodological Issues
Current Pharmaceutical Design Prevalence of Cognitive Impairment and Dementia in Malays – Epidemiology of Dementia in Singapore Study
Current Alzheimer Research Decreased Plasma Level of Lipoprotein Lipase Predicted Verbal Disfluency in Chinese Type 2 Diabetes Mellitus Patients with Early Cognitive Deficits
Current Alzheimer Research Glycosaminoglycans, Protein Aggregation and Neurodegeneration
Current Protein & Peptide Science Poly(ADP-Ribose)Polymerase 1 (PARP-1) Activation and Ca<sup>2+</sup> Permeable α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic Acid (AMPA) Channels in Post-Ischemic Brain Damage: New Therapeutic Opportunities?
CNS & Neurological Disorders - Drug Targets Medicinal Chemistry and Therapeutic Potential of Agonists, Antagonists and Allosteric Modulators of A1 Adenosine Receptor: Current Status and Perspectives
Current Pharmaceutical Design Synaptic Plasticity, Metaplasticity and Depression
Current Neuropharmacology Reduction of Myocardial Ischemia-Reperfusion Injury with Pre- and Postconditioning: Molecular Mechanisms and Therapeutic Targets
Cardiovascular & Hematological Disorders-Drug Targets