Abstract:
:Amyloid-β (Aβ) accumulation in the brain is a hallmark of Alzheimer's disease (AD) pathology. However, the molecular mechanism controlling microglial Aβ phagocytosis is poorly understood. Here we found that the E3 ubiquitin ligase Pellino 1 (Peli1) is induced in the microglia of AD-like five familial AD (5×FAD) mice, whose phagocytic efficiency for Aβ was then impaired, and therefore Peli1 depletion suppressed the Aβ deposition in the brains of 5×FAD mice. Mechanistic characterizations indicated that Peli1 directly targeted CCAAT/enhancer-binding protein (C/EBP)β, a major transcription factor responsible for the transcription of scavenger receptor CD36. Peli1 functioned as a direct E3 ubiquitin ligase of C/EBPβ and mediated its ubiquitination-induced degradation. Consequently, loss of Peli1 increased the protein levels of C/EBPβ and the expression of CD36 and thus, promoted the phagocytic ability in microglial cells. Together, our findings established Peli1 as a critical regulator of microglial phagocytosis and highlighted the therapeutic potential by targeting Peli1 for the treatment of microglia-mediated neurological diseases.
journal_name
PLoS Bioljournal_title
PLoS biologyauthors
Xu J,Yu T,Pietronigro EC,Yuan J,Arioli J,Pei Y,Luo X,Ye J,Constantin G,Mao C,Xiao Ydoi
10.1371/journal.pbio.3000837subject
Has Abstractpub_date
2020-10-05 00:00:00pages
e3000837issue
10eissn
1544-9173issn
1545-7885pii
PBIOLOGY-D-20-00092journal_volume
18pub_type
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