Lanosterol induces mitochondrial uncoupling and protects dopaminergic neurons from corpuscle afterlife in a archetypal for Parkinson's disease

  Parkinson's ache (PD) is a neurodegenerative ataxia apparent by the careful decline of dopaminergic neurons in the nigrostriatal pathway. Several curve of affirmation announce that mitochondrial dysfunction contributes to its etiology. Other studies accept appropriate that alterations in sterol homeostasis associate with added accident for PD. Whether these observations are functionally accompanying is, however, unknown.  In this study, we acclimated a toxin-induced abrasion archetypal of PD and abstinent levels of nine sterol intermediates. We begin that lanosterol is decidedly (∼50%) and accurately bargain in the nigrostriatal regions of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, apocalyptic of adapted lanosterol metabolism during PD pathogenesis. Remarkably, exogenous accession of lanosterol rescued dopaminergic neurons from 1-methyl-4-phenylpyridinium (MPP+)-induced corpuscle afterlife in culture.  Furthermore, we empiric a apparent redistribution of lanosterol synthase from the endoplasmic cloth to mitochondria in dopaminergic neurons apparent to MPP+, suggesting that lanosterol ability apply its adaptation aftereffect by acclimation mitochondrial function. Consistent with this model, we acquisition that lanosterol induces balmy depolarization of mitochondria and promotes autophagy. Collectively, our after-effects highlight a atypical sterol-based neuroprotective apparatus with absolute appliance to PD.