Landmark 4 · Discovery
First Parkinson's gene: SNCA
In short
A single amino-acid change in alpha-synuclein caused inherited Parkinson's, proving the disease can be genetic and pointing to the protein now at the centre of slowing-the-disease research.
- What it is
- Discovery
- Outcome
- Confirmed and built on
- When
- 1997
- Approach
- Clear the bad protein
- Research lane
- Synuclein misfolding & spread
- Last checked
- 19 Oct 2026
The research record
This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".
Who
Mihael Polymeropoulos, Robert Nussbaum and colleagues, Laboratory of Genetic Disease Research, National Human Genome Research Institute, NIH (20 authors in all), with Lawrence Golbe and Roger Duvoisin and Greek and Italian collaborators. The work was NIH intramural; funding is not stated in the abstract.
What happened
A mutation was found in the alpha-synuclein gene in one large Italian kindred and three unrelated Greek families with dominantly inherited Parkinson's. The change swaps alanine for threonine at position 53 (A53T; UniProt cites this paper for it). The Italian family's gene had already been mapped to chromosome 4q. The paper appeared in Science on 27 June 1997.
Why it moved us toward a cure
It proved Parkinson's can be genetic. It also pointed to the protein that is now the main target for slowing the disease: antibodies, aggregation blockers and gene-silencing drugs all trace back here.
Outcome
Advanced. Alpha-synuclein is the leading target, though no alpha-synuclein drug has yet succeeded in a trial.
Sources
- Polymeropoulos et al., Science 1997;276:2045–2047, DOI 10.1126/science.276.5321.2045 (PubMed 9197268; abstract via Europe PMC)
- UniProt P37840 (SNCA) variant A53T, citing PubMed 9197268
- Not yet verified: that everyone affected carried the change (abstract does not say; text removed); the DNA-level change; the families' sizes.
How it connects
Built on
None recorded.
Led to
- builds on Alpha-synuclein is what Lewy bodies are made of · 1997
- builds on UCHL1 I93M (PARK5) · 1998
- builds on Further SNCA point mutations · 1998
- builds on Twin study: genes matter little after age 50 · 1999
- builds on MAPT (tau) H1 haplotype · 2000
- builds on Synuclein knockout mice are viable · 2000
- builds on Drosophila synuclein model · 2000
- builds on A53T alpha-synuclein mice · 2002
- builds on Extra copies of the synuclein gene cause Parkinson's · 2003
- builds on Yeast synuclein models · 2003
- builds on Chaperone-mediated autophagy · 2004
- builds on GIGYF2 and EIF4G1: disputed genes · 2008
- builds on First GWAS: SNCA, MAPT, then 24 loci · 2009
- builds on Synuclein helps assemble synapse machinery · 2010 (link inferred)