日本秋田大學(xué)一個(gè)研究小組13日發(fā)表報(bào)告說(shuō),，他們?cè)趧?dòng)物實(shí)驗(yàn)中發(fā)現(xiàn)了腦神經(jīng)細(xì)胞死亡的部分機(jī)制。
秋田大學(xué)教授佐佐木雄彥領(lǐng)導(dǎo)的研究小組13日在英國(guó)《自然》雜志網(wǎng)絡(luò)版上發(fā)表報(bào)告說(shuō),，如果腦神經(jīng)細(xì)胞內(nèi)分解無(wú)用磷脂的酶無(wú)法發(fā)揮作用,，神經(jīng)細(xì)胞就會(huì)死亡，從而導(dǎo)致運(yùn)動(dòng)機(jī)能障礙,。
在實(shí)驗(yàn)過(guò)程中,，研究人員培育出了體內(nèi)缺乏這種酶的小鼠，結(jié)果其腦神經(jīng)細(xì)胞內(nèi)的無(wú)用磷脂無(wú)法分解,，堆積在細(xì)胞中,，導(dǎo)致細(xì)胞死亡，最終引起了小鼠身體顫抖等運(yùn)動(dòng)障礙,。
佐佐木雄彥指出,，雖然此前已經(jīng)知道這種酶的存在，但是它與腦神經(jīng)細(xì)胞死亡的關(guān)系尚不為人所知,。他們的研究表明,，可以利用這種酶開發(fā)治療阿爾茨海默氏癥、肌萎縮性側(cè)索硬化癥的方法以及減輕腦中風(fēng)后遺癥的方法等。(生物谷Bioon.com)
生物谷推薦原文出處：
Nature (2010) doi:10.1038/nature09023
The PtdIns(3,4)P2 phosphatase INPP4A is a suppressor of excitotoxic neuronal death
Junko Sasaki, Satoshi Kofuji, Reietsu Itoh, Toshihiko Momiyama, Kiyohiko Takayama, Haruka Murakami, Shinsuke Chida, Yuko Tsuya, Shunsuke Takasuga, Satoshi Eguchi, Ken Asanuma, Yasuo Horie, Kouichi Miura, Elizabeth Michele Davies, Christina Mitchell, Masakazu Yamazaki, Hirokazu Hirai, Tadaomi Takenawa, Akira Suzuki & Takehiko Sasaki
Phosphorylated derivatives of phosphatidylinositol, collectively referred to as phosphoinositides, occur in the cytoplasmic leaflet of cellular membranes and regulate activities such as vesicle transport, cytoskeletal reorganization and signal transduction1, 2. Recent studies have indicated an important role for phosphoinositide metabolism in the aetiology of diseases such as cancer, diabetes, myopathy and inflammation3, 4, 5. Although the biological functions of the phosphatases that regulate phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) have been well characterized, little is known about the functions of the phosphatases regulating the closely related molecule phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P2). Here we show that inositol polyphosphate phosphatase 4A (INPP4A), a PtdIns(3,4)P2 phosphatase, is a suppressor of glutamate excitotoxicity in the central nervous system. Targeted disruption of the Inpp4a gene in mice leads to neurodegeneration in the striatum, the input nucleus of the basal ganglia that has a central role in motor and cognitive behaviours. Notably, Inpp4a-/- mice show severe involuntary movement disorders. In vitro, Inpp4a gene silencing via short hairpin RNA renders cultured primary striatal neurons vulnerable to cell death mediated by N-methyl-d-aspartate-type glutamate receptors (NMDARs). Mechanistically, INPP4A is found at the postsynaptic density and regulates synaptic NMDAR localization and NMDAR-mediated excitatory postsynaptic current. Thus, INPP4A protects neurons from excitotoxic cell death and thereby maintains the functional integrity of the brain. Our study demonstrates that PtdIns(3,4)P2, PtdIns(3,4,5)P3 and the phosphatases acting on them can have distinct regulatory roles, and provides insight into the unique aspects and physiological significance of PtdIns(3,4)P2 metabolism. INPP4A represents, to our knowledge, the first signalling protein with a function in neurons to suppress excitotoxic cell death. The discovery of a direct link between PtdIns(3,4)P2 metabolism and the regulation of neurodegeneration and involuntary movements may aid the development of new approaches for the treatment of neurodegenerative disorders.
