Okadaic acid: a tool to study regulatory mechanisms for neurodegeneration and regeneration in Alzheimer's disease.

Abstract

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 inhibitor 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 multifactorial neurodegenerative disorder and hyperphosphorylated 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 hyperphosphorylation 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 characteristic of AD pathology (Figure 1).