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Fig. 9 | Molecular Neurodegeneration

Fig. 9

From: Hexokinases link DJ-1 to the PINK1/parkin pathway

Fig. 9

The hexokinases link DJ-1 to the PINK1/parkin pathway. a Normal signaling through the PI3K/AKT pathway. DJ-1 negatively regulates PTEN which promotes signal transduction to AKT. b PI3K/AKT signaling in the absence of DJ-1. Without negative regulation by DJ-1, PTEN inhibits signaling to AKT. c The effect of the loss of DJ-1 on PI3K/AKT/GSK-3β combined with the hallmarks of aging (e.g. deregulated nutrient sensing and mitochondrial dysfunction) leads to the buildup of HK1 in the cytosol and activation of the polyol pathway in the brains of aged rodents. d Promoting the dissociation of hexokinases from VDAC, inhibiting AKT, and decreasing hexokinase mRNA all inhibit parkin translocation to depolarized mitochondria in immortalized cells. For details regarding HK1/2 shRNA and other AKT inhibitors aside from MK2206, please see [41]

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