Amine-related neurotoxins in Parkinson's disease: past, present, and future

Parkinson's disease (PD) is an aging-related movement disorder caused by a deficiency of the neurotransmitter dopamine (DA) in the striatum of the brain as a result of selective degeneration of nigrostriatal DA neurons. The molecular basis of the cell death of DA neurons is unknown, but one hypothesis is the presence of some amine-related neurotoxins that kill specifically nigrostriatal DA neurons over a long period of time. This neurotoxin hypothesis of PD started in the 1980s when 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was discovered to produce acutely PD-like symptoms. Two groups of natural MPTP-like and amine-related neurotoxins have been investigated as endogenous candidate compounds: isoquinolines (IQs) and beta-carbolines. These neurotoxins are speculated to cause oxidative stress, mitochondrial dysfunction, apoptotic cell death, and PD symptoms. However, since PD is a neurodegenerative disorder that progresses slowly over a period of many years, a long-term study may be required to elucidate the neurotoxicity of such neurotoxins in relation to PD.