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000137741 037__ $$aDZNE-2020-04063
000137741 041__ $$aEnglish
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000137741 1001_ $$0P:(DE-HGF)0$$aToyoda, Yusuke$$b0
000137741 245__ $$aProducts of the Parkinson's disease-related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival.
000137741 260__ $$aCambridge$$bCompany$$c2014
000137741 264_1 $$2Crossref$$3online$$bThe Company of Biologists$$c2014-07-25
000137741 264_1 $$2Crossref$$3print$$bThe Company of Biologists$$c2014-08-15
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000137741 520__ $$aParkinson's disease is associated with mitochondrial decline in dopaminergic neurons of the substantia nigra. One of the genes linked with the onset of Parkinson's disease, DJ-1/PARK7, belongs to a novel glyoxalase family and influences mitochondrial activity. It has been assumed that glyoxalases fulfill this task by detoxifying aggressive aldehyde by-products of metabolism. Here we show that supplying either D-lactate or glycolate, products of DJ-1, rescues the requirement for the enzyme in maintenance of mitochondrial potential. We further show that glycolic acid and D-lactic acid can elevate lowered mitochondrial membrane potential caused by silencing PINK-1, another Parkinson's related gene, as well as by paraquat, an environmental toxin known to be linked with Parkinson's disease. We propose that DJ-1 and consequently its products are components of a novel pathway that stabilizes mitochondria during cellular stress. We go on to show that survival of cultured mesencephalic dopaminergic neurons, defective in Parkinson's disease, is enhanced by glycolate and D-lactate. Because glycolic and D-lactic acids occur naturally, they are therefore a potential therapeutic route for treatment or prevention of Parkinson's disease.
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000137741 7001_ $$0P:(DE-HGF)0$$aErkut, Cihan$$b1
000137741 7001_ $$0P:(DE-HGF)0$$aPan-Montojo, Francisco$$b2
000137741 7001_ $$0P:(DE-HGF)0$$aBoland, Sebastian$$b3
000137741 7001_ $$0P:(DE-HGF)0$$aStewart, Martin P$$b4
000137741 7001_ $$0P:(DE-HGF)0$$aMüller, Daniel J$$b5
000137741 7001_ $$0P:(DE-2719)2000028$$aWurst, Wolfgang$$b6$$udzne
000137741 7001_ $$0P:(DE-HGF)0$$aHyman, Anthony A$$b7$$eCorresponding author
000137741 7001_ $$0P:(DE-HGF)0$$aKurzchalia, Teymuras V$$b8
000137741 77318 $$2Crossref$$3journal-article$$a10.1242/bio.20149399$$b : The Company of Biologists, 2014-07-25$$n8$$p777-784$$tBiology Open$$v3$$x2046-6390$$y2014
000137741 773__ $$0PERI:(DE-600)2632264-X$$a10.1242/bio.20149399$$gVol. 3, no. 8, p. 777 - 784$$n8$$p777-784$$q3:8<777 - 784$$tBiology open$$v3$$x2046-6390$$y2014
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