Accumulation of human wild-type (wt) α-synuclein (α-syn) induces neurodegeneration in humans and in experimental rodent models of Parkinson disease (PD). It also leads to endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR). We overexpressed glucose regulated protein 78, also known as BiP (GRP78/BiP), to test the hypothesis that this ER chaperone modulates the UPR, blocks apoptosis, and promotes the survival of nigral dopamine (DA) neurons in a rat model of PD induced by elevated level of human α-syn. We determined that α-syn activates ER stress mediators associated with pancreatic ER kinase-like ER kinase (PERK) and activating transcription factor-6 (ATF6) signaling pathways as well as proaoptotic CCAAT/-enhancer-binding protein homologous protein (CHOP) in nigral DA neurons. At the same time, overexpression of GRP78/BiP diminished α-syn neurotoxicity by down regulating ER stress mediators and the level of apoptosis, promoted survival of nigral tyrosine hydroxylase (TH) positive cells and resulted in higher levels of striatal DA, while eliminating amphetamine induced behavioral asymmetry. We also detected a complex between GRP78/BiP and α-syn that may contribute to prevention of the neurotoxicity caused by α-syn. Our data suggest that the molecular chaperone GRP78/BiP plays a neuroprotective role in α-syn-induced Parkinson-like neurodegeneration.

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Bioreactors hold great promise for treating graywater in an advanced life support system for space applications. However, questions remain regarding the reproducibility and reliability of biological systems for long-term use. Although there have been numerous studies on ground-based biological systems, most studies focus on a single reactor or a simple (single carbon) waste stream. There have been very few studies on microbial communities in replicate reactors using a nonsterile, complex waste stream. In this report, we describe the characterization of five replicate denitrifying reactors receiving a complex feed, including urine and limb washes from donors at Johnson Space Center over a 100-day period. Denitrifying conditions were employed because of the ease in adding a terminal electron acceptor to the bioreactor. Bacterial populations were tracked by 16S rRNA and nosZ genes T-RFLP analysis to target the total and denitrifying microbial communities. The results demonstrated reproducible biological communities with nearly identical performance that slowly changed with time and exhibited low variability with respect to the bacterial community (T-RFLP peak area) in all reactors. These results suggest that, when designed for replication, bioreactors are not stochastic systems exhibiting chaotic behavior, but are biological systems that can be highly reproducible and reliable.