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

FEBS Lett. 2002 Jul 3;522(1-3):9-13. doi: 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 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

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

Substances

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