Drosophila synuclein model

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

Mel B. Feany and W. W. Bender (Department of Pathology, Brigham and Women's Hospital and Harvard Medical School). Nature 404:394–398, 2000. Funders were not read.

What happened

Three years after SNCA was found (landmark 4), the team made flies carrying human normal or mutant synuclein. Expressing normal and mutant human synuclein produced adult-onset loss of dopamine neurons, filamentous intraneuronal inclusions containing synuclein, and locomotor dysfunction. The authors said the fly recapitulates the essential features of the human disorder and allows a powerful genetic approach.

Why it moved us toward a cure

Flies live weeks, so thousands of genes and compounds can be tested quickly. It showed that synuclein toxicity does not need a mammal. It sits beside the mouse models of landmark 31.

Outcome

Advanced. A fly is not a mammal, so hits from fly screens need confirmation in mammalian models.

Sources

• Feany & Bender, Nature 2000, DOI 10.1038/35006074 (abstract read via Europe PMC, PMID 10746727)
• Not yet verified: neuron counts and ages in the paper body; funders; whether flies have their own synuclein gene and how closely the inclusions match Lewy bodies (not checked).