Reduced protein phosphatase 2A activity induces hyperphosphorylation and altered compartmentalization of tau in transgenic mice.

Reduced PP2A activity induces hyperphosphorylation and altered compartmentalization of tau in transgenic mice

Insulin deprivation induces PP2A inhibition and tau hyperphosphorylation in hTau mice, a model of Alzheimer’s disease-like tau pathology

Abnormally hyperphosphorylated tau aggregated as intraneuronal neurofibrillary tangles is one of the two neuropathological hallmarks of Alzheimer's disease (AD). The majority of AD cases are sporadic with numerous environmental, biological and genetic risks factors. Interestingly, insulin dysfunction and hyperglycaemia are both risk factors for sporadic AD. However, how hyperglycaemia and insul...

Silencing I2PP2A Rescues Tau Pathologies and Memory Deficits through Rescuing PP2A and Inhibiting GSK-3β Signaling in Human Tau Transgenic Mice

Increase of inhibitor-2 of protein phosphatase-2A [Formula: see text] is associated with protein phosphatase-2A (PP2A) inhibition and tau hyperphosphorylation in Alzheimer's disease (AD). Down-regulating [Formula: see text] attenuated amyloidogenesis and improved the cognitive functions in transgenic mice expressing amyloid precursor protein (tg2576). Here, we found that silencing [Formula: see...

Alterations in glucose metabolism induce hypothermia leading to tau hyperphosphorylation through differential inhibition of kinase and phosphatase activities: implications for Alzheimer's disease.

Alzheimer's disease (AD) brains contain neurofibrillary tangles (NFTs) composed of abnormally hyperphosphorylated tau protein. Regional reductions in cerebral glucose metabolism correlating to NFT densities have been reported in AD brains. Assuming that reduced glucose metabolism might cause abnormal tau hyperphosphorylation, we induced in vivo alterations of glucose metabolism in mice by starv...

Intranasal insulin prevents anesthesia-induced hyperphosphorylation of tau in 3xTg-AD mice

BACKGROUND It is well documented that elderly individuals are at increased risk of cognitive decline after anesthesia. General anesthesia is believed to be a risk factor for Alzheimer's disease (AD). Recent studies suggest that anesthesia may increase the risk for cognitive decline and AD through promoting abnormal hyperphosphorylation of tau, which is crucial to neurodegeneration seen in AD. ...