Altered Insulin Signaling in Alzheimer's Disease Brain - Special Emphasis on PI3K-Akt Pathway

Frontiers in Neuroscience
Sami GabboujTeemu Natunen


Alzheimer's disease (AD) and type 2 diabetes (T2D) are both diseases with increasing prevalence in aging populations. T2D, characterized by insulin resistance and defective insulin signaling, is a common co-morbidity and a risk factor for AD, increasing the risk approximately two to fourfold. Insulin exerts a wide variety of effects as a growth factor as well as by regulating glucose, fatty acid, and protein metabolism. Certain lifestyle factors, physical inactivity and typical Western diet (TWD) containing high fat and high sugar are strongly associated with insulin resistance and T2D. The PI3K-Akt signaling pathway is a major mediator of effects of insulin and plays a crucial role in T2D pathogenesis. Decreased levels of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) subunits as well as blunted Akt kinase phosphorylation have been observed in the AD brain, characterized by amyloid-β and tau pathologies. Furthermore, AD mouse models fed with TWD have shown to display altered levels of PI3K subunits. How impaired insulin-PI3K-Akt signaling in peripheral tissues or in the central nervous system (CNS) affects the development or progression of AD is currently poorly understood. Interestingly, enhancement of PI3K-Akt signali...Continue Reading


Jun 1, 1992·Neurochemistry International·G GuptaN Z Baquer
Aug 1, 1997·The Journal of Biological Chemistry·M Hong, V M Lee
Aug 28, 1998·Journal of Neural Transmission·L FrölichP Riederer
Dec 14, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lixia ZhaoGreg M Cole
Jul 2, 2005·Diabetes/metabolism Research and Reviews·Ake Sjöholm, Thomas Nyström
Jan 16, 2007·Neurobiology of Aging·Lisa MosconiMony J de Leon
Apr 4, 2007·Cell Metabolism·Shaohui Huang, Michael P Czech
Jul 4, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Barry BolandRalph A Nixon
Aug 30, 2008·American Journal of Physiology. Endocrinology and Metabolism·Sigalit Boura-Halfon, Yehiel Zick
Feb 6, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Myoung-Hwan KimEunjoon Kim
Mar 18, 2010·Nature Reviews. Neurology·V Hugh PerryClive Holmes
Jul 7, 2010·Cell·Mark A Lemmon, Joseph Schlessinger
Aug 10, 2010·Biological Psychiatry·Walter SwardfagerNathan Herrmann
Sep 16, 2010·Nature Reviews. Neurology·Catrina Sims-RobinsonEva L Feldman
Jan 12, 2011·Annual Review of Immunology·Margaret F Gregor, Gökhan S Hotamisligil
Feb 11, 2011·Proceedings of the National Academy of Sciences of the United States of America·Loredana StoicaMauro Costa-Mattioli
May 21, 2011·The Journal of Pathology·Ying LiuCheng-Xin Gong
Jan 10, 2012·Cold Spring Harbor Perspectives in Medicine·Alberto Serrano-PozoBradley T Hyman
Jan 17, 2012·Trends in Endocrinology and Metabolism : TEM·Bhumsoo Kim, Eva L Feldman
Jan 19, 2012·Diabetes & Metabolism·M C Calle, M L Fernandez
Mar 20, 2012·Cell·Frances M Ashcroft, Patrik Rorsman
Jun 30, 2012·Ageing Research Reviews·Ludovic MartinFaraj Terro
Jul 24, 2012·Pharmacology & Therapeutics·William A BanksMichelle A Erickson
Aug 14, 2013·Diabetes Care·Chris MoranVelandai Srikanth
Dec 20, 2013·Diabetes/metabolism Research and Reviews·Y M KhazraiP Pozzilli
Jul 22, 2014·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Auriel A WilletteBarbara B Bendlin
Jan 20, 2015·Molecular Neurobiology·Yu Tang, Weidong Le
Feb 18, 2015·Nature Immunology·Michael T HenekaEicke Latz
Dec 24, 2015·Frontiers in Cellular Neuroscience·Maria Stefania SpagnuoloLuisa Cigliano
Jan 13, 2017·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Honghua ZhengGuojun Bu
Jan 19, 2017·Nature·Shane A LiddelowBen A Barres
Jan 31, 2017·Nature Neuroscience·Eduardo R ZimmerPedro Rosa-Neto
Aug 13, 2017·Cell·Tyler K UllandMarco Colonna
Nov 29, 2017·Neuropharmacology·Colin D ChapmanChristian Benedict
Aug 5, 2018·Journal of Cellular Physiology·Xiaotian XuXiaolei Shi


May 22, 2020·Frontiers in Cellular Neuroscience·Laura Poupon-BejuitAhad A Rahim
Apr 22, 2020·Neurochemical Research·Thuy Trang NguyenVan Giau Vo
Feb 21, 2020·International Journal of Molecular Sciences·Amit Koren-ItonDaniel M Michaelson
Aug 14, 2020·International Journal of Molecular Sciences·Chunyue WangDi Wang
May 6, 2020·International Journal of Molecular Sciences·Thuy Trang NguyenVo Van Giau
Mar 21, 2020·International Journal of Molecular Sciences·Jose A SantiagoJudith A Potashkin
Dec 2, 2020·Annals of Human Genetics·David Curtis, Sreejan Bandyopadhyay
Jan 24, 2021·The Journal of Biological Chemistry·Yan-Li LiXiao-Fan Zhao

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