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Parkinson’s disease (PD) features oxidative stress and accumulation of misfolded (unfolded, alternatively folded, or mutant) proteins with associated loss of dopaminergic neurons. Oxidative stress and the accumulated misfolded proteins elicit cellular responses that include an endoplasmic reticulum (ER) stress response that may protect cells against the(More)
Alpha-synuclein is the major protein component of Lewy bodies, a cardinal pathological feature of the degenerating Parkinsonian brain. Alpha-synuclein has been reported to be able to intercalate into membranes via formation of an alpha-helical structure at its N-terminal end. Recent in vitro studies from various laboratories have demonstrated that(More)
Age-related increases in monoamine oxidase B (MAO-B) may contribute to neurodegeneration associated with Parkinson's disease (PD). The MAO-B inhibitor deprenyl, a long-standing antiparkinsonian therapy, is currently used clinically in concert with the dopamine precursor L-DOPA. Clinical studies suggesting that deprenyl treatment alone is not protective(More)
Cellular senescence is a potent anti-cancer mechanism that arrests the proliferation of mitotically competent cells to prevent malignant transformation. Senescent cells accumulate with age in a variety of human and mouse tissues where they express a complex 'senescence-associated secretory phenotype' (SASP). The SASP includes many pro-inflammatory(More)
Parkinson's disease is a neurodegenerative disorder characterized by the preferential loss of midbrain dopaminergic neurons in the substantia nigra (SN). One of the earliest detectable biochemical alterations that occurs in the Parkinsonian brain is a marked reduction in SN levels of total glutathione (glutathione plus glutathione disulfide), occurring(More)
Lithium has recently been suggested to have neuroprotective properties in relation to several neurodegenerative diseases. In this study, we examined the potential cytoprotective effect of lithium in preventing oxidative stress-induced protein accumulation and neuronal cell death in the presence of increased α-synuclein levels in vitro and in vivo.(More)
Oxidative stress and mitochondrial dysfunction have been implicated in the pathology of HD; however, the precise mechanisms by which mutant huntingtin modulates levels of oxidative damage in turn resulting in mitochondrial dysfunction are not known. We hypothesize that mutant huntingtin increases oxidative mtDNA damage leading to mitochondrial dysfunction.(More)
Alpha-synuclein has been reported to be present in the nucleus and levels enhanced by oxidative stress. Herein, we sought to investigate the mechanistic role of nuclear alpha-synuclein. We found that alpha-synuclein nuclear localization coincided with enhanced chromatin binding both in an in vitro and a corresponding in vivo brain oxidative stress model(More)
UNLABELLED Following its activation by PINK1, parkin is recruited to depolarized mitochondria where it ubiquitinates outer mitochondrial membrane proteins, initiating lysosomal-mediated degradation of these organelles. Mutations in the gene encoding parkin, PARK2, result in both familial and sporadic forms of Parkinson's disease (PD) in conjunction with(More)
Loss of parkin E3 ligase activity as a result of parkin gene mutation in rare familial forms of Parkinson's disease (PD) has been shown to be detrimental to mitochondrial function and to contribute to ensuing neurodegeneration. This has been shown by ourselves and others to be in part due to reductions in parkin-mediated ubiquitination of the(More)