美國研究人員在新一期《神經(jīng)元》（Neuron）雜志上報告說，大腦血糖含量長期緩慢降低,，可能誘發(fā)早老性癡呆癥。
美國西北大學芝加哥芬伯格醫(yī)學院的羅伯特·瓦薩等人對人類和老鼠大腦研究后發(fā)現(xiàn),，大腦血糖含量緩慢降低會導(dǎo)致大腦血流量降低,，從而使大腦能量不足。如果這種情況長期出現(xiàn),，會導(dǎo)致一種名叫elF2alpha的蛋白發(fā)生變異,，從而促成一種特定酶的形成，這種酶能引發(fā)導(dǎo)致早老性癡呆癥的大腦貝塔淀粉樣蛋白堆積,。
瓦薩說,，這一研究成果有助于開發(fā)通過抑制elF2alpha蛋白生成來治療早老性癡呆癥的藥物。
早老性癡呆癥又稱阿爾茨海默氏癥,，是最常見的老年癡呆癥,，其臨床表現(xiàn)為認知、記憶和語言功能出現(xiàn)障礙等,。研究人員認為,，人們可以通過加強鍛煉、降低膽固醇和控制血壓來提高大腦血糖含量水平,，從而改善大腦血流狀況,，預(yù)防早老性癡呆癥。（生物谷Bioon.com）
生物谷推薦原始出處：
Neuron,，Volume 60, Issue 6, 988-1009,，Tracy O'Connor，Robert Vassar
Phosphorylation of the Translation Initiation Factor eIF2 Increases BACE1 Levels and Promotes Amyloidogenesis
Tracy O'Connor1,Katherine R. Sadleir1,Erika Maus1,Rodney A. Velliquette1,Jie Zhao1,Sarah L. Cole1,William A. Eimer1,Brian Hitt1,Leslie A. Bembinster1,Sven Lammich2,Stefan F. Lichtenthaler2,Sébastien S. Hébert3,Bart De Strooper3,Christian Haass2,David A. Bennett4andRobert Vassar1,,
1 Department of Cell and Molecular Biology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
2 Department of Biochemistry, Laboratory for Neurodegenerative Disease Research, Center for Integrated Protein Science Munich and Adolf-Butenandt-Institute, Ludwig-Maximilians-University, 80539 Munich, Germany
3 Department of Molecular and Developmental Genetics, VIB, Center for Human Genetics, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium
4 Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL 60612, USA
β-site APP cleaving enzyme-1 (BACE1), the rate-limiting enzyme for β-amyloid (Aβ) production, is elevated in Alzheimer's disease (AD). Here, we show that energy deprivation induces phosphorylation of the translation initiation factor eIF2α (eIF2α-P), which increases the translation of BACE1. Salubrinal, an inhibitor of eIF2α-P phosphatase PP1c, directly increases BACE1 and elevates Aβ production in primary neurons. Preventing eIF2α phosphorylation by transfection with constitutively active PP1c regulatory subunit, dominant-negative eIF2α kinase PERK, or PERK inhibitor P58IPK blocks the energy-deprivation-induced BACE1 increase. Furthermore, chronic treatment of aged Tg2576 mice with energy inhibitors increases levels of eIF2α-P, BACE1, Aβ, and amyloid plaques. Importantly, eIF2α-P and BACE1 are elevated in aggressive plaque-forming 5XFAD transgenic mice, and BACE1, eIF2-αP, and amyloid load are correlated in humans with AD. These results strongly suggest that eIF2 αphosphorylation increases BACE1 levels and causes A βoverproduction, which could be an early, initiating molecular mechanism in sporadic AD.
