Complex I deficiency in the Parkinson's brain

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

Anthony Schapira, J. M. Cooper, D. Dexter, P. Jenner, J. B. Clark and C. D. Marsden. The 1990 paper is from the Department of Neurological Science, Royal Free Hospital School of Medicine, London (PubMed affiliation). Funders are not stated in the abstracts.

What happened

The first report was a one-page Lancet letter (1989;1:1269, 1 June 1989); the full paper followed in J Neurochem 54:823–827 in 1990. Post-mortem substantia nigra from 9 Parkinson's patients and 9 matched controls showed a specific reduction in the activity of Complex I, an enzyme in the mitochondrial energy chain. Total protein and mitochondrial mass were similar, and succinate cytochrome c reductase (another chain enzyme) was normal. The authors noted this matches the defect MPTP causes (landmark 2), pointing to a toxin-like mitochondrial cause.

Why it moved us toward a cure

It showed mitochondrial failure is part of the human disease, not just of the MPTP model. That opened the line that leads to the rotenone model (13), PINK1/parkin (12, 15) and mitophagy drugs.

Outcome

Advanced as mechanism. Mitochondria-protective drugs have not yet worked clinically (the CoQ10 QE3 trial is covered in a later batch). Mitophagy drugs are in early trials (see landmark 15).

Sources

• Schapira et al., Lancet 1989 (letter), DOI 10.1016/S0140-6736(89)92366-0 (PMID 2566813; citation and author list confirmed in PubMed; no abstract available)
• Schapira et al., J Neurochem 1990;54:823–827, DOI 10.1111/j.1471-4159.1990.tb02325.x (PMID 2154550; 9 vs 9 sample and findings from the PubMed abstract)
• Not yet verified: the oft-quoted percentage reduction (left out, abstract gives none); the independent 1989 reports from other groups; the Lancet letter's content (no abstract).