The role of UCH-L1 in autophagy and mitochondrial turnover
OA Version
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Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder caused by both environmental and genetic factors. Ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) genetic mutations have been implicated in PD pathogenesis, potentially due to changes in autophagy. Recent reports suggest that autophagy is not affected when mitochondrial UCH-L1 is inhibited, reflected by the autophagy marker, microtubule-associated protein 1 light chain 3, or LC3. However, these experiments discount the fact that autophagy is not static, but a dynamic cycle that must be measured appropriately (Cartier et al, 2012). Using this as the driving force of my study, I suppressed autophagy with the lysosomal inhibitor bafilomycin in addition to inhibiting UCH-L1. Using an insulinoma cell line, a neuroblastoma cell line, and primary neurons, I illustrate that LC3-II levels rise due to an increase in autophagic flux and not because of a decrease in autophagosome clearance. These findings also shed light on how UCH-L1 can be studied as a future target for PD prevention and treatment with respect to autophagy.
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Thesis (M.A.)--Boston University