Abstract
We investigated the pathological relevance of the "Aβ oligomer (AβO) cascade hypothesis" in 3xTg-AD mice. This study was also designed to elucidate the molecular mechanism underlying the toxic action of AβOs. To target the extracellular AβOs in vivo, a monoclonal antibody specific for AβOs was developed using a novel method. Monoclonal 72D9 was intravenously administered to aged 3xTg-AD mice bearing the human AD pathology to investigate the relevance of the AβO cascade hypothesis. To further identify the AβO-binding molecule on the cell surface, small interfering RNA (siRNA) for sortilin was transfected into SH-SY5Y cells. The sortilin-dependent molecular mechanism underlying toxic action of AβOs and/or AβO endocytosis was also assessed in cultured cortical neurons forming synapses. The 72D9 immunotherapy of aged 3xTg-AD mice revealed that extracellular and intraneuronal AβOs are related, and that intraneuronal AβOs act upstream of tau. We also found that extracellular AβOs first act as a sortilin ligand, and then induce p75(NTF)-mediated apoptosis, endocytosis-induced attenuation of autophagy, or accumulation of AβOs in autophagosomes. Taken together, these findings provide novel lines of evidence that sortilin governs the tox...Continue Reading
References
Mar 1, 1996·Neurobiology of Aging·T KawarabayashiS Hirai
Oct 4, 1996·Science·K HsiaoG Cole
Apr 5, 2002·Nature·Dominic M WalshDennis J Selkoe
Jul 19, 2002·Nature·Hilal A LashuelPeter T Lansbury
Oct 26, 2002·Science·Dennis J Selkoe
May 15, 2003·The Journal of Comparative Neurology·Philippe SarretAlain Beaudet
Aug 5, 2003·Neuron·Salvatore OddoFrank M LaFerla
Oct 8, 2003·Current Drug Targets. CNS and Neurological Disorders·Shivanand P LadElliott J Mufson
Nov 5, 2003·Biochemistry·Brett A ChromyWilliam L Klein
Feb 27, 2004·Nature·Anders NykjaerClaus M Petersen
Dec 21, 2004·Nature Neuroscience·James P ClearyKaren H Ashe
Mar 8, 2005·Neuron·Lauren M BillingsFrank M LaFerla
Jul 16, 2005·Proceedings of the National Academy of Sciences of the United States of America·Arjan QuistRatnesh Lal
Mar 17, 2006·Nature·Sylvain LesnéKaren H Ashe
May 5, 2007·Science·Erik D RobersonLennart Mucke
Dec 23, 2008·The Journal of Biological Chemistry·Rakez KayedCharles Glabe
Jan 16, 2009·PloS One·Daijun LingPaul M Salvaterra
May 15, 2010·The Journal of Biological Chemistry·Philip J Dolan, Gail V W Johnson
Citations
Jul 25, 2013·International Journal of Molecular Sciences·Yi XiaLiang-Wei Chen
Jul 22, 2014·Alzheimer's Research & Therapy·William F GoureFranz Hefti
Aug 19, 2015·Neurobiology of Disease·Qian MaBarbara L Hempstead
Jun 16, 2015·Frontiers in Cellular Neuroscience·Sergio T FerreiraFernanda G De Felice
Jan 22, 2015·Acta Neuropathologica·Kirsten L Viola, William L Klein
May 31, 2018·Journal of Alzheimer's Disease : JAD·Erika N ClineWilliam L Klein
Apr 25, 2018·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Shu-Yin XuXiao-Xin Yan
Jan 6, 2018·Circulation Research·Jaume AmengualEdward A Fisher
May 11, 2013·Neuroreport·Fan ZengYan-Jiang Wang
Jul 31, 2013·Journal of Neurochemistry·Khalil SaadipourXin-Fu Zhou
Apr 26, 2013·The Biochemical Journal·Maddalena Costanzo, Chiara Zurzolo
May 12, 2020·Wiley Interdisciplinary Reviews. Developmental Biology·Amrita PathakBruce D Carter
Mar 28, 2019·Annual Review of Biochemistry·Jaime Vaquer-Alicea, Marc I Diamond
Nov 7, 2019·Scientific Reports·Stefania FornerFrank M LaFerla
Jul 10, 2016·Journal of Alzheimer's Disease : JAD·Carl-Henrik AnderssonPetronella Kettunen
Oct 8, 2021·Biological Chemistry·Simone EggertTanja Brigadski