Mechanism of specific dopaminergic neuronal death in Parkinson's disease

Norio Ogawa, Masato Asanuma, K. Miyoshi

Research output: Contribution to journalReview article

4 Citations (Scopus)

Abstract

Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic (DAergic) neurons of the nigrostriatal system, with resulting reduction in striatal dopamine (DA) concentration. Various mechanisms have been implicated in the pathogenesis and progression of PD. Among them, mitochondrial dysfunction, inflammation and oxidative stress had been accepted as the most plausible mechanism of disease progression. The free radicals/oxidative stress produced by MPTP, 6-hydroxydopamine, rotenone, activated microglias, and disturbances in mitochondrial respiratory enzymes provide a common pathway for the progression of all kinds of neurons. On the other hand, numerous studies on DA-induced neurotoxicity have been reported recently, and DA itself exerts cytotoxicity in DAergic neurons mainly due to the generation of highly reactive DA -quinones which are DAergic neuron-specific cytotoxic molecules. DA quinones may irreversibly alter protein function through the formation 5-cysteinyl-dopamine on the protein. For example, the formation of DA quinone-alpha-synuclein complex consequently increases cytotoxic protofibrils and covalent modification of functional enzymes. Thus, DA quinones play an important role in 'specific' DAergic neuro-degeneration of PD.

Original languageEnglish
Pages (from-to)1629-1634
Number of pages6
JournalNippon rinsho. Japanese journal of clinical medicine
Volume62
Issue number9
Publication statusPublished - Sep 2004

ASJC Scopus subject areas

  • Medicine(all)

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