Amino acid determinants of alpha-synuclein aggregation: putting together pieces of the puzzle.

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 alpha-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 alpha-synuclein play a crucial role in the pathogenesis of the synucleinopathies. However, the molecular mechanisms underlying alpha-synuclein aggregation into specific filamentous inclusions remained unknown until recently. Data on the aggregation and fibrillation properties of human alpha-, beta- and gamma-synucleins, mouse alpha-synuclein and familial Parkinson's disease mutants of human alpha-synuclein (A30P and A53T) are analyzed in order to shed light on the amino acid determinants of synuclein aggregation.

• Authors: Vladimir N Uversky, Anthony L Fink
• Journal: FEBS letters (FEBS Lett) Vol. 522 Issue 1-3 Pg. 9-13 (Jul 03 2002) ISSN: 0014-5793 [Print] England
• PMID: 12095610 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Amino Acids
• Nerve Tissue Proteins
• SNCA protein, human
• Snca protein, mouse
• Synucleins
• alpha-Synuclein

Topics

• Amino Acid Sequence
• Amino Acids
• Animals
• Humans
• Mice
• Molecular Sequence Data
• Nerve Tissue Proteins (metabolism)
• Sequence Analysis, Protein
• Synucleins
• alpha-Synuclein