Abstract:
:It is widely believed that the nigrostriatal toxicity of MPTP is due to its oxidation by brain monoamine oxidase first to MPDP+, and eventually to MPP+. Following uptake by the synaptic dopamine reuptake system, it is concentrated in the matrix of striatal mitochondria by an energy-dependent carrier, energized by the electrical gradient of the membrane. At the very high intramitochondrial concentrations thus reached, MPP+ combines with NADH dehydrogenase at a point distal to its iron-sulfur clusters but prior to the Q10 combining site. This leads to cessation of oxidative phosphorylation, ATP depletion, and cell death. Other pyridine derivatives act similarly on NADH dehydrogenase but they are not acutely toxic unless concentrated by the MPP+ carrier.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Singer TP,Ramsay RR,McKeown K,Trevor A,Castagnoli NE Jrdoi
10.1016/0300-483x(88)90169-2subject
Has Abstractpub_date
1988-04-01 00:00:00pages
17-23issue
1eissn
0300-483Xissn
1879-3185pii
0300-483X(88)90169-2journal_volume
49pub_type
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