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.
Nagatsu
Toshiharu
T
Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, 470-1192, Japan. tnagatsu@fujita-hu.ac.jp
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives / Q000737:chemistry; D000588:Amines / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002243:Carbolines / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000633:toxicity; D017072:Neostriatum / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009498:Neurotoxins / Q000737:chemistry / Q000633:toxicity*; D010300:Parkinson Disease / Q000378:metabolism / Q000503:physiopathology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology
D000588:Amines; D002243:Carbolines; D007546:Isoquinolines; D009498:Neurotoxins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine