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
-
In Silico Studies in Drug Research Against Neurodegenerative Diseases
Current Neuropharmacology Genetic Markers in Biological Fluids for Aging-Related Major Neurocognitive Disorder
Current Alzheimer Research Neuroprotection and Sex Steroid Hormones: Evidence of Estradiol- Mediated Protection in Hypertensive Encephalopathy
Mini-Reviews in Medicinal Chemistry Modulation of Energy Intake and Expenditure Due to Habitual Physical Exercise
Current Pharmaceutical Design Discovery of New Cardiovascular Hormones for the Treatment of Congestive Heart Failure
Cardiovascular & Hematological Disorders-Drug Targets Molecular and Biochemical Features in Alzheimers Disease
Current Pharmaceutical Design The Origins of Aging: Evidence that Aging is an Adaptive Phenotype
Current Aging Science Translating Genetic Findings into Therapy in Parkinson Disease
Recent Patents on CNS Drug Discovery (Discontinued) Neuronal Ceroid Lipofuscinosis: The Increasing Spectrum of an Old Disease
Current Molecular Medicine Cutting through the Complexities of mTOR for the Treatment of Stroke
Current Neurovascular Research Nephrotoxicity of Bisphenol A (BPA) -An Updated Review
Current Molecular Pharmacology Diagnosis, Pathogenesis and Therapeutic Targets in Amyotrophic Lateral Sclerosis
CNS & Neurological Disorders - Drug Targets Expansion of Umbilical Cord Blood for Clinical Transplantation
Current Stem Cell Research & Therapy Effect of Brain-Derived Neurotrophic Factor (BDNF) Gene Variants on the Therapeutic Response and the Risk for Mood Disorders
Current Pharmacogenomics and Personalized Medicine Autologous Fat Transfer and Cell-Based Strategies for Soft Tissue Reconstruction
Current Tissue Engineering (Discontinued) Resilience to Alzheimer's Disease: The Role of Physical Activity
Current Alzheimer Research Etiopathogenesis, Classical Immunotherapy and Innovative Nanotherapeutics for Inflammatory Neurological Disorders
Current Nanoscience Recent Advances in the Rationale Design of GPER Ligands
Current Medicinal Chemistry Neuroinflammation is Associated with Brain Extracellular TAU-Protein Release After Spontaneous Subarachnoid Hemorrhage
Current Drug Targets New Insights into Biological Markers of Frontotemporal Lobar Degeneration Spectrum
Current Medicinal Chemistry