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|Title:||Lanosterol is a survival factor for dopaminergic neurons||Authors:||LIM LYNETTE||Keywords:||Lipids, Parkinson's Diseases, Lanosterol, neurons||Issue Date:||15-Jul-2011||Citation:||LIM LYNETTE (2011-07-15). Lanosterol is a survival factor for dopaminergic neurons. ScholarBank@NUS Repository.||Abstract:||Parkinson?s disease (PD) is a neurodegenerative disorder, marked by the selective degeneration of dopaminergic neurons in the nigrostriatal pathway. Several lines of evidence indicate that mitochondrial dysfunction contributes to its etiology. Other studies have suggested that alterations in sterol homeostasis correlate with increased risk for PD. Whether these observations are functionally related is, however, unknown. In this study, I used a toxin-induced mouse model of PD and measured levels of nine sterol intermediates. I found that lanosterol is significantly (~50%) and specifically reduced in the nigrostriatal regions of MPTP-treated mice, indicative of altered lanosterol metabolism during PD pathogenesis. Remarkably, exogenous addition of lanosterol rescued dopaminergic neurons from MPP+-induced cell death in culture. Furthermore, there is a marked redistribution of lanosterol synthase (LSS) from the endoplasmic reticulum (ER) to mitochondria in dopaminergic neurons exposed to MPP+, suggesting of that lanosterol might exert its survival effect by regulating mitochondria function. Consistent with this model, I find that lanosterol induces mild depolarization of mitochondria and promotes autophagy. Collectively, these results highlight a novel sterol-based neuroprotective mechanism with direct relevance to PD.||URI:||http://scholarbank.nus.edu.sg/handle/10635/30302|
|Appears in Collections:||Ph.D Theses (Open)|
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