Alkaloids, alcohol and Parkinson's disease

Relatively early seminal investigations on 'mammalian alkaloid biosynthesis'-endogenous Pictet-Spengler condensations of catecholamines or indoleamines with aldehydes (such as acetaldehyde from ethanol metabolism) to form tetrahydroisoquinoline or beta-carboline alkaloids-and the roles of mammalian alkaloids in the CNS complications of chronic alcoholism were launched in Gerald Cohen's laboratory. While occasional studies on alcohol and the alkaloids continue today, the field of study has been expanded principally by others into Parkinson's disease. Certain mammalian or xenobiotic alkaloids have been examined by various laboratories as possible neurotoxic factors inducing mitochondrial energy depletion and/or oxidative stress in the nigrostriatum. In that regard, specific arguments for N-methylated 'MPP(+)-like' cationic alkaloids that can be generated centrally from beta-carbolines derived from the environment and diet are summarized.