Okadaic acid: Okadaic acid (OKA), a polyether (C38 fatty acid) toxin, is a potent and selective inhibitor of protein phosphatase, PP1 and protein phosphatase 2A (PP2A). It is mainly extracted from a black spong...Okadaic acid: Okadaic acid (OKA), a polyether (C38 fatty acid) toxin, is a potent and selective inhibitor of protein phosphatase, PP1 and protein phosphatase 2A (PP2A). It is mainly extracted from a black sponge Hallichondria okadaii and has been suggested to play a potent probe for studying the various molecular, cellular, biochemical and mechanism of neurotoxicity. It is known as a selective and potent in- hibitor of serine/threonine phosphatases 1 and 2A induces hyperphosphorylation of tau in vitro and in vivo. It has been reported that Alzheimer's disease (AD) is a complex multi- factorial neurodegenerative disorder and hyperphosphor- ylated tau protein is a major pathological hallmark of AD. The reduced activity of phosphatases like, PP2A has been implicated in the brain of AD patients. OKA also induced inhibition of protein phosphatases cause neurofibrillary tangles (NFTs) like pathological changes and tau hyperphos- phorylation seen in AD pathology. Our and others reports inferred that OKA induces neurodegeneration along with tau hyperphosphorylation, GSK3β activation, oxidative stress, neuroinflammation and neurotoxicity which are char- acteristic of AD pathology (Figure 1).展开更多
基金supported in part by Council of Scientific and Industrial Research(CSIR),IndiaNational Institute of Health,USA
文摘Okadaic acid: Okadaic acid (OKA), a polyether (C38 fatty acid) toxin, is a potent and selective inhibitor of protein phosphatase, PP1 and protein phosphatase 2A (PP2A). It is mainly extracted from a black sponge Hallichondria okadaii and has been suggested to play a potent probe for studying the various molecular, cellular, biochemical and mechanism of neurotoxicity. It is known as a selective and potent in- hibitor of serine/threonine phosphatases 1 and 2A induces hyperphosphorylation of tau in vitro and in vivo. It has been reported that Alzheimer's disease (AD) is a complex multi- factorial neurodegenerative disorder and hyperphosphor- ylated tau protein is a major pathological hallmark of AD. The reduced activity of phosphatases like, PP2A has been implicated in the brain of AD patients. OKA also induced inhibition of protein phosphatases cause neurofibrillary tangles (NFTs) like pathological changes and tau hyperphos- phorylation seen in AD pathology. Our and others reports inferred that OKA induces neurodegeneration along with tau hyperphosphorylation, GSK3β activation, oxidative stress, neuroinflammation and neurotoxicity which are char- acteristic of AD pathology (Figure 1).