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Toyoda, Y.* ; Erkut, C.* ; Pan-Montojo, F.* ; Boland, S.* ; Stewart, M.P.* ; Müller, D.J.* ; Wurst, W. ; Hyman, A.A.* ; Kurzchalia, T.V.*

Products of the Parkinson's disease-related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival.

Biol. Open 3, 777-784 (2014)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
Parkinson'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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter D-lactate ; Glycolate ; Glyoxalase ; Mitochondrial Membrane Potential ; Parkinson's Disease; Oxidative Stress; Alpha-synuclein; Caenorhabditis-elegans; Escherichia-coli; Enteric Neurons; Paraquat; Pink1; Cells; Methylglyoxal; Drosophila-pink1
e-ISSN 2046-6390
Zeitschrift Biology Open
Quellenangaben Band: 3, Heft: 8, Seiten: 777-784 Artikelnummer: , Supplement: ,
Verlag Company of Biologists
Verlagsort Cambridge
Begutachtungsstatus Peer reviewed