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1.  Protein phosphatase 5 protects neurons against amyloid β toxicity 
Journal of neurochemistry  2009;111(2):391-402.
Amyloid β (Aβ) is thought to promote neuronal cell loss in Alzheimer’s disease (AD), in part through the generation of reactive oxygen species (ROS) and subsequent activation of mitogen-activated protein kinase (MAPK) pathways. Protein phosphatase 5 (PP5) is a ubiquitously expressed serine/threonine phosphatase which has been implicated in several cell stress response pathways and shown to inactivate MAPK pathways through key dephosphorylation events. Therefore we examined whether PP5 protects dissociated embryonic rat cortical neurons in vitro from cell death evoked by Aβ. As predicted, neurons in which PP5 expression was decreased by siRNA treatment were more susceptible to Aβ toxicity. In contrast, overexpression of PP5, but not the inactive PP5 mutant, H304Q, prevented MAPK phosphorylation and neurotoxicity induced by Aβ. PP5 also prevented cell death caused by direct treatment with H2O2, but did not prevent Aβ-induced production of ROS. Thus, the neuroprotective effect of PP5 requires its phosphatase activity and lies downstream of Aβ-induced generation of ROS. In summary, our data indicate that PP5 plays a pivotal neuroprotective role against cell death induced by Aβ and oxidative stress. Consequently, PP5 might be an effective therapeutic target in AD and other neurodegenerative disorders in which oxidative stress is implicated.
doi:10.1111/j.1471-4159.2009.06337.x
PMCID: PMC3044491  PMID: 19686245
PP5; protein phosphatase 5; amyloid β; Alzheimer’s disease; neuroprotection; oxidative stress

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