近日，美國亞利桑那州太陽城老年健康研究所華人科學家申勇博士等發(fā)現(xiàn),，阿爾茨海默?。ˋD）患者的祖細胞生成神經(jīng)元的能力受限，可能是由于β連接素（β catenin）信號轉(zhuǎn)導通路被β淀粉樣蛋白（Aβ）干擾,。相關(guān)論文發(fā)表于美國《神經(jīng)科學雜志》（J Neurosci 2009,，29（20）：6545）。
AD可破壞大腦的神經(jīng)元,，影響人的認知功能,。雖然近來研究顯示，健康人新皮質(zhì)中的祖細胞可以“生產(chǎn)”新生神經(jīng)元,，但AD患者的祖細胞是否有此功能,，尚不可知。
申勇博士等通過比較健康對照者和AD患者皮質(zhì)中的膠質(zhì)祖細胞（GPC）,，發(fā)現(xiàn)AD患者的GPC更新能力和神經(jīng)發(fā)生能力減弱,。進一步研究發(fā)現(xiàn)，與健康對照者相比,，AD患者的GPC中糖原合酶激酶3β（GSK-3β,，一種可催化β連接素磷酸化的酶——編者注）水平更高，而且伴隨著磷酸化β連接素的水平升高,。用Aβ處理健康對照者的GPC,，可使其生成新生神經(jīng)元的能力喪失，還導致β連接素的信號轉(zhuǎn)導蛋白發(fā)生變化,，與AD患者腦中所見相同,。
申勇博士認為，該結(jié)果說明,，取自AD患者腦皮質(zhì)的干細胞可能不具有神經(jīng)發(fā)生的能力,，因而無法用于AD的治療。但β連接素的信號轉(zhuǎn)導通路與神經(jīng)發(fā)生有關(guān),，或許可成為治療AD的靶點,。（生物谷Bioon.com）
生物谷推薦原始出處：
The Journal of Neuroscience, May 20, 2009, 29(20):6545-6557; doi:10.1523/JNEUROSCI.0421-09.2009
Interruption of β-Catenin Signaling Reduces Neurogenesis in Alzheimer's Disease
Ping He and Yong Shen
Haldeman Laboratory of Molecular and Cellular Neurobiology, Sun Health Research Institute, Sun City, Arizona 85351
The neuronal loss associated with Alzheimer's disease (AD) affects areas of the brain that are vital to cognition. Although recent studies have shown that new neurons can be generated from progenitor cells in the neocortices of healthy adults, the neurogenic potential of the stem/progenitor cells of AD patients is not known. To answer this question, we compared the properties of glial progenitor cells (GPCs) from the cortices of healthy control (HC) and AD subjects. The GPCs from AD brain samples displayed reduced renewal capability and reduced neurogenesis compared with GPCs from HC brains. To investigate the mechanisms underlying this difference, we compared β-catenin signaling proteins in GPCs from AD versus HC subjects and studied the effect of amyloid β peptide (Aβ, a hallmark of AD pathology) on GPCs. Interestingly, GPCs from AD patients exhibited elevated levels of glycogen synthase kinase 3β (GSK-3β, an enzyme known to phosphorylate β-catenin), accompanied by an increase in phosphorylated β-catenin and a decrease in nonphosphorylated β-catenin compared with HC counterparts. Furthermore. we found that Aβ treatment impaired the ability of GPCs from HC subjects to generate new neurons and caused changes in β-catenin signaling proteins similar to those observed in GPCs from AD patients. Similar results were observed in GPCs isolated from AD transgenic mice. These results suggest that Aβ-induced interruption of β-catenin signaling may contribute to the impairment of neurogenesis in AD progenitor cells.
