Anatomic and Disease Specificity of NADH CoQ₁ Reductase (Complex I) Deficiency in Parkinson's Disease

TLDR

MPTP induces parkinsonism by inhibiting complex I, and recent findings of complex I deficiency in the substantia nigra of Parkinson’s disease patients link this mitochondrial defect to the idiopathic disease. The study demonstrates that complex I deficiency in Parkinson’s disease is anatomically specific to the substantia nigra and absent in another neurodegenerative disorder affecting the same region. The data show no association between L‑DOPA treatment and complex I deficiency, supporting the hypothesis that this mitochondrial defect underlies dopaminergic neuron loss in Parkinson’s disease.

Abstract

Abstract: 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) is thought to produce parkinsonism in humans and other primates through its inhibition of complex I. The recent discovery of mitochondrial complex I deficiency in the substantia nigra of patients with Parkinson's disease has provided a remarkable link between the idiopathic disease and the action of the neurotoxin MPTP. This article shows that complex I deficiency in Parkinson's disease is anatomically specific for the substantia nigra, and is not present in another neurodegenerative disorder involving the substantia nigra. Evidence is also provided to show that there is no correlation between l‐3,4‐dihydroxyphenylalanine therapy and complex I deficiency. These results suggest that complex I deficiency may be the underlying cause of dopaminergic cell death in Parkinson's disease.