Presenilin 1 phosphorylation regulates amyloid-β degradation by microglia Journal Article


Authors: Ledo, J. H.; Liebmann, T.; Zhang, R.; Chang, J. C.; Azevedo, E. P.; Wong, E.; Silva, H. M.; Troyanskaya, O. G.; Bustos, V.; Greengard, P.
Article Title: Presenilin 1 phosphorylation regulates amyloid-β degradation by microglia
Abstract: Amyloid-β peptide (Aβ) accumulation in the brain is a hallmark of Alzheimer’s Disease. An important mechanism of Aβ clearance in the brain is uptake and degradation by microglia. Presenilin 1 (PS1) is the catalytic subunit of γ-secretase, an enzyme complex responsible for the maturation of multiple substrates, such as Aβ. Although PS1 has been extensively studied in neurons, the role of PS1 in microglia is incompletely understood. Here we report that microglia containing phospho-deficient mutant PS1 display a slower kinetic response to micro injury in the brain in vivo and the inability to degrade Aβ oligomers due to a phagolysosome dysfunction. An Alzheimer’s mouse model containing phospho-deficient PS1 show severe Aβ accumulation in microglia as well as the postsynaptic protein PSD95. Our results demonstrate a novel mechanism by which PS1 modulates microglial function and contributes to Alzheimer’s -associated phenotypes. © 2020, The Author(s).
Journal Title: Molecular Psychiatry
Volume: 26
Issue: 10
ISSN: 1359-4184
Publisher: Nature Publishing Group  
Date Published: 2021-10-01
Start Page: 5620
End Page: 5635
Language: English
DOI: 10.1038/s41380-020-0856-8
PUBMED: 32792660
PROVIDER: scopus
PMCID: PMC7881060
DOI/URL:
Notes: Article -- Export Date: 1 February 2022 -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Wan Fung Wong
    12 Wong