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, 2011). Misregulated biogenesis has been implicated to underlie pathological conditions in a number of neurodegenerative diseases. A host of proteins such as VDAC, cytochrome C, POLG, TFAM and PGC-1��, NRF-1 are known to regulate mitochondrial biogenesis, and differential expression of these proteins has been reported in various neurodegenerative disorders. Our array data did not show substantive differences in expression of these mitochondrial biogenesis genes between PARK2 patients and controls, indicating that the phenotype was not caused by mitochondrial biogenesis. Deletion and overreplication of mtDNA are emerging as important factors underlying the selective loss of dopaminergic LY294002 price neurons during aging and in PD (Anderson et?al., 1981; Ekstrand et?al., 2007; Johns, 1995; Wei, 1998). Although we did not detect any changes in mtDNA copy numbers between healthy and diseased samples, the mitochondria-to-cell-volume fraction, an important parameter of mitochondrial membrane potential (Birket et?al., 2011), was significantly reduced in PARK2 dopaminergic neurons. A decrease in mitochondrial membrane potential in PARK2-deficient cells could make a selective population of cells more vulnerable to stress Lapatinib in vitro stimuli. Consistent with this, PARK2 mutant Drosophila have been reported to accumulate depolarized mitochondria in dopaminergic neurons (Burman et?al., 2012). Indeed, a decline mitochondrial membrane potential has been reported in PD patient derived fibroblasts, with PARK2 deficiency (Mortiboys et?al., 2008). Our results are consistent S6 Kinase with previous reports of the action of PARK2 and reduction in TH-positive cells described in mouse PARK2 KO model (Perier et?al., 2013; Reeve et?al., 2013; Rothfuss et?al., 2009) and consistent with work done in the fly model. The mitochondrial phenotype was not seen when we examined the total cells in the culture; rather, it was only seen in TH-positive dopaminergic neurons, which represented only a small percentage of the total cells (