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MSDC 0160 act as an insulin sensitizer and a modulator of mitochondrial pyruvate carrier (MPC), a key controller of cellular metabolism that influences mTOR (mammalian target of rapamycin) activation. In Vitro: MSDC-0160 acts as insulin sensitizers without activating PPARγ. MSDC-0160 (10 μM) pretreatment (1 hour) prevents the MPP+ (10 μM)-induced loss of both tyrosine hydroxylase (TH)-immunoreactive differentiated Lund human mesencephalic (LUHMES) cells. MSDC-0160 protects only TH-immunoreactive neurons, which is consistent with the selected concentration of MPP+ primarily being toxic to dopamine neurons. In addition, MSDC-0160 counteracts both MPP+-induced shortening of neurite length and reduces branching in both LUHMES cells. MSDC-0160 (10 or 100 μM) prevents the loss of GFP-fluorescent dopaminergic neurons induced by MPP+ (0.75 mM) in nematodes (P =0.0001), whereas 1 μM MSDC-0160 does not. MSDC-0160 (10 μM) blocks LPS-induced increases in iNOS expression in BV2 cell lysates. MSDC-0160 is mainly to prevent the activation of mTOR produced by the metabolic changes rather than to directly inhibit mTOR kinase activity[1]. PPARγ sparing TZD, MSDC-0160, reduces resistance in the insulin/IGF-1 signaling pathway and restores IGF-1-induced akt phosphorylation. MSDC-0160 (10-20 μM) in conbination with IGF-1 prevents the loss of insulin content and maintains insulin secretion. Treatment of human islets with MSDC-0160 (1-50 μM) activates AMPK and downregulates mTOR. MSDC-0160 (1-50 μM) treatment maintains human β-cell phenotype[2]. The combined treatment with PPARγ ligands (MSDC 0160) and γ-radiation synergistically induces caspase-dependent apoptotic cell death, and PPARγ ligands significantly enhance the γ-radiation-induced DNA damage response in a PPARγ-independent manner[3].In Vivo: MSDC-0160 (30 mg/kg per day, p.o.) can be observed in plasma and brain tissue of the mice, proving MSDC-0160 can effectively enter the brain. MSDC-0160 (30 mg/kg per day, p.o.) treatment 3 days after MPTP injection, improves motor behavior, protects nigrostriatal neurons, and suppresses disease progression in the MPTP mouse model of Parkinson’s disease (PD), improves motor behavior in the open-field and rotarod tests in the En1+/- genetic mouse model of PD, and prevents dopaminergic neurodegeneration in the En1+/- genetic mouse model of PD. MSDC-0160 (30 mg/kg, p.o.) modulates mTOR signaling in C. elegans and the MPTP mouse model of PD. MSDC-0160 down-regulates mTOR signaling and restores autophagy in the En1+/- genetic mouse model of PD[1].