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Upregulation of GPR109A in Parkinson’s Disease

Background Anecdotal animal and human studies have implicated the symptomatic and neuroprotective roles of niacin in Parkinson’s disease (PD). Niacin has a high affinity for GPR109A, an anti-inflammatory receptor. Niacin is also thought to be involved in the regulation of circadian rhythm. Here we evaluated the relationships among the receptor, niacin levels and EEG night-sleep...

Resistance to MPTP-Neurotoxicity in α-Synuclein Knockout Mice Is Complemented by Human α-Synuclein and Associated with Increased β-Synuclein and Akt Activation

. doi:10.1371/journal.pone.0016706 Resistance to MPTP-Neurotoxicity in a-Synuclein Knockout Mice Is Complemented by Human a-Synuclein and Associated with Increased b-Synuclein and Akt Activation Bobby

Conditional transgenic mice expressing C-terminally truncated human α-synuclein (αSyn119) exhibit reduced striatal dopamine without loss of nigrostriatal pathway dopaminergic neurons

Background Missense mutations and multiplications of the α-synuclein gene cause autosomal dominant familial Parkinson's disease (PD). α-Synuclein protein is also a major component of Lewy bodies, the hallmark pathological inclusions of PD. Therefore, α-synuclein plays an important role in the pathogenesis of familial and sporadic PD. To model α-synuclein-linked disease in vivo...

Conditional transgenic mice expressing C-terminally truncated human α-synuclein (αSyn119) exhibit reduced striatal dopamine without loss of nigrostriatal pathway dopaminergic neurons

Missense mutations and multiplications of the α-synuclein gene cause autosomal dominant familial Parkinson's disease (PD). α-Synuclein protein is also a major component of Lewy bodies, the hallmark pathological inclusions of PD. Therefore, α-synuclein plays an important role in the pathogenesis of familial and sporadic PD. To model α-synuclein-linked disease in vivo, transgenic...

Neuroprotective Effects of the Triterpenoid, CDDO Methyl Amide, a Potent Inducer of Nrf2-Mediated Transcription

The NF-E2-related factor-2 (Nrf2)/antioxidant response element (ARE) signaling pathway regulates phase 2 detoxification genes, including a variety of antioxidative enzymes. We tested neuroprotective effects of the synthetic triterpenoid CDDO-MA, a potent activator of the Nrf2/ARE signaling. CDDO-MA treatment of neuroblastoma SH-SY5Y cells resulted in Nrf2 upregulation and...

Dopaminergic Neuronal Loss, Reduced Neurite Complexity and Autophagic Abnormalities in Transgenic Mice Expressing G2019S Mutant LRRK2

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene cause late-onset, autosomal dominant familial Parkinson's disease (PD) and also contribute to idiopathic PD. LRRK2 mutations represent the most common cause of PD with clinical and neurochemical features that are largely indistinguishable from idiopathic disease. Currently, transgenic mice expressing wild-type or disease...

Mitochondrial localization of the Parkinson's disease related protein DJ-1: implications for pathogenesis

Both homozygous (L166P, M26I, deletion) and heterozygous mutations (D149A, A104T) in the DJ-1 gene have been identified in Parkinson's disease (PD) patients. The biochemical function and subcellular localization of DJ-1 protein have not been clarified. To date the localization of DJ-1 protein has largely been described in studies over-expressing tagged DJ-1 protein in vitro. It...

Stress-induced alterations in parkin solubility promote parkin aggregation and compromise parkin's protective function

Mutations in parkin are currently recognized as the most common cause of familial Parkinsonism. Emerging evidence also suggests that parkin expression variability may confer a risk for the development of the more common, sporadic form of Parkinson's disease (PD). Supporting this, we have recently demonstrated that parkin solubility in the human brain becomes altered with age. As...