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Neuronal ApoE Regulates the Cell-to-Cell Transmission of α-Synuclein

Authors
Kang, SJ | Kim, SJ  | Noh, HR | Kim, BJ | Kim, JB | Jin, U  | Park, SA  | Park, SM
Citation
International journal of molecular sciences, 23(15). : 8311-8311, 2022
Journal Title
International journal of molecular sciences
ISSN
1661-65961422-0067
Abstract
The presence of protein inclusions, called Lewy bodies (LBs) and Lewy neurites (LNs), in the brain is the main feature of Parkinson's disease (PD). Recent evidence that the prion-like propagation of alpha-synuclein (alpha-syn), as a major component of LBs and LNs, plays an important role in the progression of PD has gained much attention, although the molecular mechanism remains unclear. In this study, we evaluated whether neuronal ApoE regulates the cell-to-cell transmission of alpha-syn and explored its molecular mechanism using in vitro and in vivo model systems. We demonstrate that neuronal ApoE deficiency attenuates both alpha-syn uptake and release by downregulating LRP-1 and LDLR expression and enhancing chaperone-mediated autophagy activity, respectively, thereby contributing to alpha-syn propagation. In addition, we observed that alpha-syn propagation was attenuated in ApoE knockout mice injected with pre-formed mouse alpha-syn fibrils. This study will help our understanding of the molecular mechanisms underlying alpha-syn propagation.
Keywords

MeSH

DOI
10.3390/ijms23158311
PMID
35955451
Appears in Collections:
Journal Papers > Research Organization > Brain Disease Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Cardiology
Journal Papers > School of Medicine / Graduate School of Medicine > Anatomy
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Ajou Authors
김, 수정  |  박, 상면  |  박, 선아  |  진, 우람
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