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Alvarez-Fischer 2013 J Neurochem
Coupling states LEAK  + , OXPHOS  +
Diseases Parkinson's  +
Has abstract The uricosuric agent probenecid is co-admi
The uricosuric agent probenecid is co-administered with the dopaminergic neurotoxin MPTP to produce a chronic mouse model of Parkinson's disease. It has been proposed that probenecid serves to elevate concentrations of MPTP in the brain by reducing renal elimination of the toxin. However, this mechanism has never been formally demonstrated to date and is questioned by our previous data showing that intracerebral concentrations of MPP+ , the active metabolite of MPTP, are not modified by co-injection of probenecid. In this study, we investigated the potentiating effects of probenecid ''in vivo'' and ''in vitro'' arguing against the possibility of altered metabolism or impaired renal elimination of MPTP. We find that probenecid (i) is toxic in itself to several neuronal populations apart from dopaminergic neurons, and (ii) that it also potentiates the effects of other mitochondrial complex I inhibitors such as rotenone. On a mechanistic level, we show that probenecid is able to lower intracellular ATP concentrations and that its toxic action on neuronal cells can be reversed by extracellular ATP. Probenecid can potentiate the effect of mitochondrial toxins due to its impact on ATP metabolism and could therefore be useful to model atypical parkinsonian syndromes.
to model atypical parkinsonian syndromes.  +
Has info [ PMID: 23802648];[ PDF]  +
Has publicationkeywords ATP  + , MPP +  + , MPTP  + , Parkinson's disease  + , Mitochondria  + , Probenecid  +
Has title Alvarez-Fischer D, Noelker C, Grünewald A,
Alvarez-Fischer D, Noelker C, Grünewald A, Vulinović F, Guerreiro S, Fuchs J, Lu L, Lombès A, Hirsch EC, Oertel WH, Michel PP, Hartmann A (2013) Probenecid potentiates MPTP/MPP+ toxicity by interference with cellular energy metabolism. J Neurochem 127:782-92.
energy metabolism. J Neurochem 127:782-92.  +
Mammal and model Mouse  +
MiP area Respiration  + , mt-Medicine  +
Pathways N  + , ROX  +
Was published in journal J Neurochem +
Was published in year 2013  +
Was written by Alvarez-Fischer D + , Noelker C + , Gruenewald A + , Vulinovic F + , Guerreiro S + , Fuchs J + , Lu L + , Lombes A + , Hirsch EC + , Oertel WH + , Michel PP + , Hartmann A +
Has processing error
"Has processing error" is a predefined property provided by Semantic MediaWiki and represents errors that appeared in connection with improper value annotations or input processing.
Alvarez-Fischer 2013 J Neurochem +
Categories Publications
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
12:12:11, 12 October 2017  +
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