2016
DOI: 10.1126/scitranslmed.aag2210
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Abstract: Mitochondrial and autophagic dysfunction as well as neuroinflammation are involved in the pathophysiology of Parkinson's disease (PD). We hypothesized that targeting the mitochondrial pyruvate carrier (MPC), a key controller of cellular metabolism that influences mTOR (mammalian target of rapamycin) activation, might attenuate neurodegeneration of nigral dopaminergic neurons in animal models of PD. To test this, we used MSDC-0160, a compound that specifically targets MPC, to reduce its activity. MSDC-0160 prot… Show more

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Cited by 149 publications
(112 citation statements)
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“…In the subacute model, mice receive five consecutive doses of MPTP 25 mg/kg i.p. (Ghosh et al., ). The subacute model causes less acute lethality and the loss of dopaminergic phenotype is more consistent.…”
Section: Neurotoxin‐induced Modelsmentioning
confidence: 99%
“…In the subacute model, mice receive five consecutive doses of MPTP 25 mg/kg i.p. (Ghosh et al., ). The subacute model causes less acute lethality and the loss of dopaminergic phenotype is more consistent.…”
Section: Neurotoxin‐induced Modelsmentioning
confidence: 99%
“…However, the toxicity of rapamycin makes it a poor candidate for development as a disease‐modifying drug in PD. A recent study showed that MSDC‐0160, which is an inhibitor of the mitochondrial pyruvate carrier that was originally developed for type II diabetes, also is an effective inhibitor of the mammalian target of rapamycin by altering cellular metabolism . By inhibiting the mitochondrial pyruvate carrier, neuronal α‐synuclein toxicity is reduced in a Caenorhabditis elegans model.…”
Section: Therapeutic Approaches Targeting α‐Synucleinmentioning
confidence: 99%
“…Recently, a mitochondrial pyruvate carrier (MPC) inhibitor, MSDC‐0160, has been also tested in different models of PD . In an α‐syn‐based Caenorhabditis elegans model, MSDC‐0160 reduced α‐syn toxicity, preventing neuronal loss.…”
Section: The Alp As a Possible Therapeutic Target For Pdmentioning
confidence: 99%
“…In an α‐syn‐based Caenorhabditis elegans model, MSDC‐0160 reduced α‐syn toxicity, preventing neuronal loss. In mice treated with 1‐methyl‐4‐phenylpyridinium (MPP+), MSDC‐0160 modulated mTOR signaling and protected against the insult caused by this neurotoxin . Furthermore, in MPTP‐treated mice, administration of MSDC‐0160 protected nigrostriatal neurons, reduced neuroinflammation, and improved locomotor behavior.…”
Section: The Alp As a Possible Therapeutic Target For Pdmentioning
confidence: 99%