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[P205]: Dissecting the function of PPP2R2B in neurogenesis and its implication in neurodegenerative diseases
Author(s) -
Su M.T.,
Yeh P.A.
Publication year - 2006
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/j.ijdevneu.2006.09.265
Subject(s) - neurogenesis , library science , citation , function (biology) , psychology , neuroscience , gerontology , medicine , computer science , biology , evolutionary biology
PPP2R2B, a brain-specific regulatory subunits of the protein phosphatase 2A (PP2A), modulates the subcellular localization and substrate specificity of the holoenzyme. Elevated expression of PPP2R2B has been postulated to be associated with autosomal dominant spinocerebellar ataxia type 12 (SCA12), while down-regulation of PP2A/and or PPP2R2B leads to Alzheimer’s disease (AD) and tauopathy. Twins (tws), a Drosophila homolog of PPP2R2B, is also exhibits neuronal specific expression pattern. We reason that function of PPP2R2B and twins may be well conserved evolutionary, and characterizing the function of twins in neurogenesis of flies may provide insightful information regarding the pathogenesis of SCA12, AD and tauopathy. We and others have found that mutation of tws causes neurological and behaviour defects in fly. In addition, we have shown that tws exerts its function cell-autonomously. Central nerves system such as brain lobes and ventral cord was withering in the absence of tws. And up-regulation of tws has been shown to have deteriorated effects on many neuronal tissues of flies. As mentioned above PP2A activity was greatly reduced in brains of individual with Alzheimer’s disease, and tauopathy is the hallmark of Alzheimer’s disease at late stages. Since microtubule-associated protein tau is one of the substrate of PP2A, we reasoned that ectopic twins or PPP2R2B expression may ameliorate tau mediated neuronal toxicity. Indeed tauopathy can be rescued by the expression of twins or human PPP2R2B. These observations suggest that Drosophila represents the pathogenic nature of above mentioned neurodegenerative disorders very well, which could serve as an excellent model for delineating the genetics pathways that lead to these neurodegenerative disorders.