TY  - JOUR
AU  - Toyoda, Yusuke
AU  - Erkut, Cihan
AU  - Pan-Montojo, Francisco
AU  - Boland, Sebastian
AU  - Stewart, Martin P
AU  - Müller, Daniel J
AU  - Wurst, Wolfgang
AU  - Hyman, Anthony A
AU  - Kurzchalia, Teymuras V
TI  - Products of the Parkinson's disease-related glyoxalase DJ-1, D-lactate and glycolate, support mitochondrial membrane potential and neuronal survival.
JO  - Biology open
VL  - 3
IS  - 8
SN  - 2046-6390
CY  - Cambridge
PB  - Company
M1  - DZNE-2020-04063
SP  - 777-784
PY  - 2014
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:25063200
C2  - pmc:PMC4133730
DO  - DOI:10.1242/bio.20149399
UR  - https://pub.dzne.de/record/137741
ER  -