Abstract
Extracellular fibrous amyloid deposits or intracellular inclusion bodies containing abnormal protein fibrils characterize many different neurodegenerative diseases, including Alzheimers disease (AD), Parkinsons disease (PD), dementia with Lewy bodies, multiple system atrophy, Huntingtons disease, and the transmissible ‘prion’; dementias. There is strong evidence from genetic, transgenic mouse and biochemical studies to support the idea that the accumulation of protein aggregates in the brain plays a seminal role in the pathogenesis of these diseases. How monomeric proteins ultimately convert to highly polymeric deposits is unknown. However, studies employing, synthetic, cell-derived and purified recombinant proteins suggest that amyloid proteins first come together to form soluble low n-oligomers. Further association of these oligomers results in higher molecular weight assemblies including so-called ‘protofibrils’ and ‘ADDLs’ and these eventually exceed solubility limits until, finally, they are deposited as amyloid fibrils. With particular reference to AD and PD, we review recent evidence that soluble oligomers are the principal pathogenic species that drive neuronal dysfunction.
Keywords: alzheimer, neurodegeneration, amyloid, synuclein, aggregation
Protein & Peptide Letters
Title: Oligomers on the Brain: the Emerging Role of Soluble Protein Aggregates in Neurodegeneration.
Volume: 11 Issue: 3
Author(s): Dominic M. Walsh and Dennis J. Selkoe
Affiliation:
Keywords: alzheimer, neurodegeneration, amyloid, synuclein, aggregation
Abstract: Extracellular fibrous amyloid deposits or intracellular inclusion bodies containing abnormal protein fibrils characterize many different neurodegenerative diseases, including Alzheimers disease (AD), Parkinsons disease (PD), dementia with Lewy bodies, multiple system atrophy, Huntingtons disease, and the transmissible ‘prion’; dementias. There is strong evidence from genetic, transgenic mouse and biochemical studies to support the idea that the accumulation of protein aggregates in the brain plays a seminal role in the pathogenesis of these diseases. How monomeric proteins ultimately convert to highly polymeric deposits is unknown. However, studies employing, synthetic, cell-derived and purified recombinant proteins suggest that amyloid proteins first come together to form soluble low n-oligomers. Further association of these oligomers results in higher molecular weight assemblies including so-called ‘protofibrils’ and ‘ADDLs’ and these eventually exceed solubility limits until, finally, they are deposited as amyloid fibrils. With particular reference to AD and PD, we review recent evidence that soluble oligomers are the principal pathogenic species that drive neuronal dysfunction.
Export Options
About this article
Cite this article as:
Walsh M. Dominic and Selkoe J. Dennis, Oligomers on the Brain: the Emerging Role of Soluble Protein Aggregates in Neurodegeneration., Protein & Peptide Letters 2004; 11 (3) . https://dx.doi.org/10.2174/0929866043407174
DOI https://dx.doi.org/10.2174/0929866043407174 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
- 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
-
Advances in Treating the Ischaemic Diabetic Foot
Current Vascular Pharmacology What Fans the Fire: Insights into Mechanisms of Leptin in Metabolic Syndrome- Associated Heart Diseases
Current Pharmaceutical Design Atrial Fibrillation in Patients Undergoing Surgical Revascularization: An Update on Pharmacologic Prophylaxis
Cardiovascular & Hematological Agents in Medicinal Chemistry Potentiating the Naturally Occurring Process for Repair of Damaged Heart
Current Pharmaceutical Design Phosphorylation-Dephosphorylation Imbalance of Cytoskeletal Associated Proteins in Neurodegenerative Diseases
Recent Patents on CNS Drug Discovery (Discontinued) Immunity to Bacterial Infections
Current Immunology Reviews (Discontinued) Neurobiology of Bipolar Disorder: Abnormalities on Cognitive and Cortical Functioning and Biomarker Levels
CNS & Neurological Disorders - Drug Targets Emerging Concepts in the Analysis of Mitochondrial Genome Instability
Current Genomics Serum Vitamin D and Cingulate Cortex Thickness in Older Adults: Quantitative MRI of the Brain
Current Alzheimer Research Cancer Preventive Phytochemicals as Speed Breakers in Inflammatory Signaling Involved in Aberrant COX-2 Expression
Current Cancer Drug Targets Motor and Non-Motor Features of Parkinson’s Disease – A Review of Clinical and Experimental Studies
CNS & Neurological Disorders - Drug Targets Natural Compounds and Plant Extracts as Therapeutics Against Chronic Inflammation in Alzheimer's Disease - A Translational Perspective
CNS & Neurological Disorders - Drug Targets Aging Changes in Satellite Cells and Their Functions
Current Aging Science Concentration-Dependent Bimodal Effect of Specific 18 kDa Translocator Protein (TSPO) Ligands on Cell Death Processes Induced by Ammonium Chloride: Potential Implications for Neuropathological Effects Due to Hyperammonemia
CNS & Neurological Disorders - Drug Targets Herbal Drug use in Sickle Cell Disease Management; Trends and Perspectives in Sub-Saharan Africa - A Systematic Review
Current Drug Discovery Technologies Exploring Spike Protein as Potential Target of Novel Coronavirus and to Inhibit the Viability Utilizing Natural Agents
Current Drug Targets Pluripotent Stem Cells for Livestock Health and Production
Current Stem Cell Research & Therapy Molecular Mechanisms, Proteinopathies and Therapeutic Strategies in Neurodegenerative Disorders
Current Genomics Disruption of Circadian Rhythms and Sleep in Critical Illness and its Impact on the Development of Delirium
Current Pharmaceutical Design The FDG-PET Revolution of Medical Imaging – Four Decades and Beyond
Current Molecular Imaging (Discontinued)