Synphilin-1 associates with alpha-synuclein and promotes the formation of cytosolic inclusions

Nat Genet. 1999 May;22(1):110-4. doi: 10.1038/8820.


Parkinson disease (PD) is a neurodegenerative disease characterized by tremor, bradykinesia, rigidity and postural instability. Post-mortem examination shows loss of neurons and Lewy bodies, which are cytoplasmic eosinophilic inclusions, in the substantia nigra and other brain regions. A few families have PD caused by mutations (A53T or A30P) in the gene SNCA (encoding alpha-synuclein). Alpha-synuclein is present in Lewy bodies of patients with sporadic PD, suggesting that alpha-synuclein may be involved in the pathogenesis of PD. It is unknown how alpha-synuclein contributes to the cellular and biochemical mechanisms of PD, and its normal functions and biochemical properties are poorly understood. To determine the protein-interaction partners of alpha-synuclein, we performed a yeast two-hybrid screen. We identified a novel interacting protein, which we term synphilin-1 (encoded by the gene SNCAIP). We found that alpha-synuclein interacts in vivo with synphilin-1 in neurons. Co-transfection of both proteins (but not control proteins) in HEK 293 cells yields cytoplasmic eosinophilic inclusions.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain Chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Chromosomes, Human, Pair 5 / genetics
  • Female
  • Humans
  • Inclusion Bodies / metabolism*
  • Lewy Bodies / metabolism
  • Male
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Plasmids / genetics
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Saccharomyces cerevisiae / genetics
  • Sequence Homology, Amino Acid
  • Synucleins
  • Tissue Distribution
  • Tissue Extracts / metabolism
  • Transfection
  • alpha-Synuclein


  • Carrier Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • SNCA protein, human
  • SNCAIP protein, human
  • Snca protein, rat
  • Sncaip protein, rat
  • Synucleins
  • Tissue Extracts
  • alpha-Synuclein

Associated data

  • GENBANK/AF076929