Effects of the mutations Ala30 to Pro and Ala53 to Thr on the physical and morphological properties of alpha-synuclein protein implicated in Parkinson's disease

FEBS Lett. 1998 Nov 27;440(1-2):67-70. doi: 10.1016/s0014-5793(98)01419-7.


Alpha-synuclein (alpha-syn) protein has been found in association with the pathological lesions of a number of neurodegenerative diseases. Recently, mutations in the alpha-syn gene have been reported in families susceptible to an inherited form of Parkinson's disease. We report here that human wild-type alpha-syn, PD-linked mutant alpha-syn(Ala30Pro) and mutant alpha-syn(Ala53Thr) proteins can self-aggregate and form amyloid-like filaments. The mutant alpha-syn forms more beta-sheet and mature filaments than the wild-type protein. These findings suggest that accumulation of alpha-syn as insoluble deposits of amyloid may play a major role in the pathogenesis of these neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution*
  • Amyloid
  • Benzothiazoles
  • Biopolymers / metabolism
  • Circular Dichroism
  • Dimerization
  • Humans
  • Hydrogen-Ion Concentration
  • Lewy Bodies
  • Microscopy, Electron
  • Mutation
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / ultrastructure
  • Parkinson Disease / etiology
  • Parkinson Disease / genetics*
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / ultrastructure
  • Synucleins
  • Thiazoles
  • alpha-Synuclein


  • Amyloid
  • Benzothiazoles
  • Biopolymers
  • Nerve Tissue Proteins
  • Recombinant Proteins
  • SNCA protein, human
  • Synucleins
  • Thiazoles
  • alpha-Synuclein
  • thioflavin T