Amino acid determinants of α‐synuclein aggregation: putting together pieces of the puzzle
Open Access
- 3 June 2002
- journal article
- review article
- Published by Wiley in FEBS Letters
- Vol. 522 (1-3) , 9-13
- https://doi.org/10.1016/s0014-5793(02)02883-1
Abstract
Parkinson's disease is the second most common neurodegenerative disease, and results from loss of dopaminergic neurons in the substantia nigra. The aggregation and fibrillation of α‐synuclein in the form of intracellular proteinaceous aggregates (Lewy bodies and Lewy neurites) have been implicated as a causative factor in this disease, as well as in several other neurodegenerative disorders, including dementia with Lewy bodies, Lewy body variant of Alzheimer's disease, multiple system atrophy and Hallervorden–Spatz disease. Thus, the aggregated forms of α‐synuclein play a crucial role in the pathogenesis of the synucleinopathies. However, the molecular mechanisms underlying α‐synuclein aggregation into specific filamentous inclusions remained unknown until recently. Data on the aggregation and fibrillation properties of human α‐, β‐ and γ‐synucleins, mouse α‐synuclein and familial Parkinson's disease mutants of human α‐synuclein (A30P and A53T) are analyzed in order to shed light on the amino acid determinants of synuclein aggregation.Keywords
This publication has 50 references indexed in Scilit:
- Biophysical Properties of the Synucleins and Their Propensities to FibrillateJournal of Biological Chemistry, 2002
- Conformational properties of α-synuclein in its free and lipid-associated states 1 1Edited by P. E. WrightJournal of Molecular Biology, 2001
- Fiber diffraction of synthetic α-synuclein filaments shows amyloid-like cross-β conformationProceedings of the National Academy of Sciences, 2000
- Aggregates from mutant and wild‐type α‐synuclein proteins and NAC peptide induce apoptotic cell death in human neuroblastoma cells by formation of β‐sheet and amyloid‐like filamentsFEBS Letters, 1998
- Synthetic filaments assembled from C‐terminally truncated α‐synucleinFEBS Letters, 1998
- α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodiesProceedings of the National Academy of Sciences, 1998
- Stabilization of α-Synuclein Secondary Structure upon Binding to Synthetic MembranesJournal of Biological Chemistry, 1998
- AlaSOPro mutation in the gene encoding α-synuclein in Parkinson's diseaseNature Genetics, 1998
- Mutation in the α-Synuclein Gene Identified in Families with Parkinson's DiseaseScience, 1997
- NACP, A Protein Implicated in Alzheimer's Disease and Learning, Is Natively UnfoldedBiochemistry, 1996