α-Synuclein Oligomers Induce a Unique Toxic Tau Strain

Biological Psychiatry
Diana L Castillo-CarranzaRakez Kayed

Abstract

The coexistence of α-synuclein and tau aggregates in several neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease, raises the possibility that a seeding mechanism is involved in disease progression. To further investigate the role of α-synuclein in the tau aggregation pathway, we performed a set of experiments using both recombinant and brain-derived tau and α-synuclein oligomers to seed monomeric tau aggregation in vitro and in vivo. Brain-derived tau oligomers were isolated from well-characterized cases of progressive supranuclear palsy (n = 4) and complexes of brain-derived α-synuclein/tau oligomers isolated from patients with Parkinson's disease (n = 4). The isolated structures were purified and characterized by standard biochemical methods, then injected into Htau mice (n = 24) to assess their toxicity and role in tau aggregation. We found that α-synuclein induced a distinct toxic tau oligomeric strain that avoids fibril formation. In vivo, Parkinson's disease brain-derived α-synuclein/tau oligomers administered into Htau mouse brains accelerated endogenous tau oligomer formation concurrent with increasing cell loss. Our findings provide evidence, for the first time, that α-synuclein enhances ...Continue Reading

Citations

Oct 28, 2019·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Baiping RenJie Zheng
Sep 6, 2019·Journal of Medical Genetics·Lei MouPedro Fernandez-Funez
Oct 24, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·Hideki HayakawaKousuke Baba
Oct 3, 2020·Brain Communications·Masami Masuda-SuzukakeMasato Hasegawa
Sep 19, 2019·Cellular and Molecular Life Sciences : CMLS·Ye TianZhentao Zhang
Apr 30, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Somin KwonEliezer Masliah
Sep 22, 2020·Brain Communications·Diana L Castillo-Carranza
May 3, 2018·Acta Neuropathologica Communications·Melissa C WrenKerstin Sander
Sep 13, 2018·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Urmi Sengupta, Rakez Kayed
Dec 14, 2019·Scientific Reports·Filippa Lo CascioRakez Kayed
Aug 12, 2020·Acta Neuropathologica Communications·Kathleen M FarmerRakez Kayed
Oct 23, 2020·The Journal of Experimental Medicine·Fares BassilVirginia M-Y Lee
Aug 2, 2020·The Journal of Biological Chemistry·Filippa Lo CascioRakez Kayed
Dec 1, 2020·Biophysical Chemistry·Magdalena I IvanovaAyyalusamy Ramamoorthy
Nov 21, 2020·International Journal of Molecular Sciences·Xiao-Yu DuRui-Tian Liu
Nov 19, 2020·Brain Sciences·Antonio Dominguez-MeijideTiago Fleming Outeiro
Apr 3, 2021·Biochemical and Biophysical Research Communications·Alimohammad HojjatianKwang Hun Lim

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Methods Mentioned

BETA
dot blot
enzyme-linked immunosorbent assay
biosensor

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