LAUSR

In 1983, Langston et al first reported chronic parkinsonism in individuals following self-injection of intravenous heroin contaminated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This astute clinical observation and subsequent work led to the discovery of MPTP as a dopaminergic neurotoxin that resulted in the development of the most validated and successful preclinical model of any neurological disease. The MPTP primate and subsequent MPTP rodent models have enabled a better understanding of basal ganglia circuitry and revolutionized translational drug discoveries and surgical treatments for Parkinson’s disease (PD). In addition, knowledge of the conversion of MPTP to 1-methyl-4-phenylpyridinium (MPP+) via monoamine-oxidase (MAO) B (MAO-B) inhibition opened up the notion of environmental toxins as potential causes of PD as well as the role of mitochondria in PD pathophysiology.