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gaobin
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Nov 26 2013, 03:48 AM
Post #1
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Nike Free Runs hermes outlet 26 billion of its debts
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Nike Free RuN AuStralia This was the first demonstration of the existence of an autophagy pathway in mammalian system independent of mTOR. The autophagyinducing ability of lithium was due to inhibition of inositol monophosphatase (IMPase), which prevents inositol recycling, leading to depletion of cellular inositol and inhibition of the phosphoinositol cycle.30, 44, 45 Likewise, L690 a specific IMPase inhibitor, induced autophagy and mimicked the effects of lithium on the clearance of autophagy substrates.30 Consistent with a role of IP3 on autophagy, a recent study by Kroemer and coworkers46 has shown that genetic knockdown or pharmacological inhibition of the IP3 receptor (IP3R) induces autophagy.Although lithium has been used for decades for treating bipolar disorder patients, its mechanism of action is still not fully understood. Inositol depletion is one of the most widely accepted hypotheses for its therapeutic action.47 It is tempting to speculate whether the beneficial effects of inositollowering agents used in the treatment of bipolar disorder are mediated by the clearance of longlived autophagy substrates (this does not implicate protein aggregation is a feature of this disease), as lithium has acute effects on free inositol levels before showing clinical effects.48 This idea48 has recently been followed up in a study that demonstrated antidepressant effects of rapamycin in rat and mouse models, leading to the suggestion that autophagy inducers may be helpful in the treatment of these disorders.49The autophagyinducing effects of lithium facilitated the clearance of mutant huntingtin in HD cell models, and reduced mutant proteinassociated aggregation and toxicity.30 Lithium also reduced neurodegeneration in HD Drosophila models.31 However, lithium is likely to have various antiapoptotic effects by inhibiting another intracellular target, glycogen synthase kinase3 (GSK3 resulting in upregulation.50, 51, 52 A recent study by Fornai and coworkers21 has shown a striking effect of lithium in increasing survival and attenuating the disease progression in ALS patients and mouse models.
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