The Role of MAPK's Signaling in Mediating ApoE4-Driven Pathology In Vivo

Current Alzheimer Research
Shiran Salomon-ZimriDaniel M Michaelson

Abstract

Alzheimer's Disease (AD) is associated with impairments in key brain Mitogen- Activated Protein Kinase (MAPK) signaling cascades including the p38, c-Jun N-terminal kinase (JNK), ERK and Akt pathways. Apolipoprotein E4 (ApoE4) is the most prevalent genetic risk factor of AD. To investigate the extent to which the MAPK signaling pathway plays a role in mediating the pathological effects of apoE4 and can be reversed by experimental manipulations. Measurements of total level and activation of MAPK signaling pathway factors, obtained utilizing immunoblot assay of hippocampal tissues from naïve and viral-treated apoE3 and apoE4 targeted replacement mice. ApoE4 mice showed robust activation of the stress related p38 and JNK pathways and a corresponding decrease in Akt activity, which is coupled to activation of GSK3β and tau hyperphosphorylation. There was no effect on the ERK pathway. We have previously shown that the apoE4- related pathology, namely; accumulation of Aβ, hyper-phosphorylated tau, synaptic impairments and decreased VEGF levels can be reversed by up-regulation of VEGF level utilizing a VEGF-expressing adeno-associated virus. Utilizing this approach, we assessed the extent to which the AD-hallmark and synaptic patholog...Continue Reading

References

Jun 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·C L MastersK Beyreuther
Jan 1, 1996·Annual Review of Medicine·A D Roses
Apr 27, 1999·Journal of Neurochemistry·K HensleyG Bing
Apr 17, 2002·American Journal of Alzheimer's Disease and Other Dementias·Hitohi Okazawa, Steven Estus
Feb 5, 2003·Neuro-Signals·Xiongwei ZhuMark A Smith
Oct 14, 2003·Experimental Neurology·Anyang SunGuoying Bing
Sep 15, 2004·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Gen KusakaJohn H Zhang
Mar 19, 2005·Journal of Neurochemistry·Hyang-Sook HoeG William Rebeck
Mar 24, 2005·Journal of Cellular and Molecular Medicine·Gang SongShideng Bao
Dec 24, 2005·Blood·Yanzheng Liu, Albert Deisseroth
Apr 11, 2006·Journal of Neuroinflammation·Izumi MaezawaKathleen S Montine
Aug 15, 2006·Brain Research·Hyang-Sook HoeG William Rebeck
Aug 18, 2006·Journal of Alzheimer's Disease : JAD·Eliezer MasliahLawrence Hansen
Aug 18, 2006·Journal of Alzheimer's Disease : JAD·Akihiko Takashima
May 8, 2007·Biochimica Et Biophysica Acta·Ana Cuenda, Simon Rousseau
Dec 20, 2007·Journal of Neurochemistry·Claudie HooperSimon Lovestone
Aug 15, 2009·Neuron·Jungsu KimDavid M Holtzman
Dec 3, 2009·Neuropharmacology·Lenka Munoz, Alaina J Ammit
Jun 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Ying ChenJoachim Herz
Jun 28, 2011·Neurobiology of Aging·Julie E SimpsonUNKNOWN MRC Cognitive Function and Ageing Neuropathology Study Group
Dec 12, 2012·Neuron·Robert W Mahley, Yadong Huang
Oct 2, 2013·Neuro-degenerative Diseases·Shiran Salomon-ZimriDaniel M Michaelson
Nov 21, 2013·Current Alzheimer Research·Moran Gilat-FrenkelDaniel M Michaelson
Dec 3, 2013·Brain Imaging and Behavior·Leo UngarMichael D Greicius
Sep 14, 2014·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Daniel M Michaelson
Feb 19, 2015·Archives of Toxicology·Eun Kyung Kim, Eui-Ju Choi
Apr 5, 2016·Current Alzheimer Research·Ishai LuzDaniel M Michaelson
Jul 4, 2016·Journal of Alzheimer's Disease : JAD·Shiran Salomon-ZimriDaniel M Michaelson
Jul 28, 2016·Lipids in Health and Disease·Janina DoseGerald Rimbach
Aug 29, 2016·Journal of Alzheimer's Disease : JAD·Anat Boehm-CaganDaniel M Michaelson
Aug 29, 2016·Neurochemical Research·Ewelina Majewska, Monika Szeliga
Sep 13, 2016·Trends in Immunology·Michal Schwartz, Aleksandra Deczkowska
Jan 7, 2017·Trends in Endocrinology and Metabolism : TEM·Courtney Lane-Donovan, Joachim Herz

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Feb 23, 2020·International Journal of Molecular Sciences·Amit Koren-ItonDaniel M Michaelson

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