PR55Bbeta的表現異常，長久以來一直被認為是小腦萎縮12型的致病原因。隨後的研究指出，PR55Bbeta的表現量增加，極可能是小腦萎縮12型的致病原因。然而，可以模擬小腦萎縮12型的動物模式，一直沒被建立，以其在生物體內的致病機轉仍不明確。在本研究實驗中，PR55Bbeta過渡表現的果蠅模式被建立，而且其果蠅表現出運動力下降和神經病變的特徵。在研究PR55Bbeta和Tau蛋白之間的作用時，我意外的利用果蠅背甲上毛的數目，建立一個新穎的模式系統，可以穩定的檢測出Tau蛋白的磷酸化程度。研究期間，我更發現，磷酸化的Tau蛋白，有保護神經的功能，並且延長果蠅的壽命。相反的，無法磷酸的Tau蛋白，對神經的發育有不好的影響。最後，本研究也指出，PP2A的B次單元與細胞骨架的調控有關，為一個新發現的嶄新的功能。也許這些研究成果，可以連結小腦萎縮12型和阿茲海默症之間致病機轉的關連。

Misregulated PR55Bβ, a B regulatory subunit of protein phosphotase 2A (PP2A), has long been documented to be associated with spinocerebellar ataxia type 12 (SCA12). Mounting evidence has shown that overexpression of PR55Bβ might be the plausible cause of SCA12. However, the pathogenic animal model of SCA12 remains absent and needs to be established to underline its pathomechanism in vivo. In this study, it has been shown that overexpression of PR55Bβ in flies led to severely retarded locomotion activity and aberrant neuronal morphology. During the investigation of the genetic interaction between PR55Bβ and Tau, I hit upon a novel notum assay system for robustly assessing phosphorylation of Tau. Further investigations revealed that hyperphosphorylated Tau might protect and somehow benefit the adult aging flies resulting in longer life-span. Conversely, both hypophosphorylated Tau and overexpression of PR55Bβ exerted detrimental effects on the dendritic outgrowth and resulted in slow locomotion activity and shortened life-span. Finally, I demonstrated that actin polymerization is positively regulated by Drosophila PP2A-B subunit, opening a new frontier for the role played of PP2A in the regulation of actin cytoskeleton. These studies might provide a link between the pathogenesis of Alzheimer’s disease and SCA12.

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