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A selective ER-phagy exerts neuroprotective effects via modulation of α-synuclein clearance in parkinsonian models

Authors
 Dong Yeol Kim  ;  Jin Young Shin  ;  Ji Eun Lee  ;  Ha Na Kim  ;  Seok Jong Chung  ;  Han Soo Yoo  ;  Sang Jin Kim  ;  Hwa Jin Cho  ;  Eun-Jae Lee  ;  Soo Jeong Nam  ;  Seong Heon Kim  ;  Jaewon Jang  ;  Seung Eun Lee  ;  Phil Hyu Lee 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.120(37) : e2221929120, 2023-09 
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN
 0027-8424 
Issue Date
2023-09
MeSH
Autophagy ; Endoplasmic Reticulum ; Humans ; Neuroprotective Agents* ; Parkinson Disease* ; alpha-Synuclein
Keywords
ER-phagy ; FAM137B ; Parkinson’s disease ; protection ; α-synuclein
Abstract
The endoplasmic reticulum (ER) is selectively degraded by ER-phagy to maintain cell homeostasis. α-synuclein accumulates in the ER, causing ER stress that contributes to neurodegeneration in Parkinson's disease (PD), but the role of ER-phagy in α-synuclein modulation is largely unknown. Here, we investigated the mechanisms by which ER-phagy selectively recognizes α-synuclein for degradation in the ER. We found that ER-phagy played an important role in the degradation of α-synuclein and recovery of ER function through interaction with FAM134B, where calnexin is required for the selective FAM134B-mediated α-synuclein clearance via ER-phagy. Overexpression of α-synuclein in the ER of the substantia nigra (SN) resulted in marked loss of dopaminergic neurons and motor deficits, mimicking PD characteristics. However, enhancement of ER-phagy using FAM134B overexpression in the SN exerted neuroprotective effects on dopaminergic neurons and recovered motor performance. These data suggest that ER-phagy represents a specific ER clearance mechanism for the degradation of α-synuclein.
Full Text
https://www.pnas.org/doi/10.1073/pnas.2221929120
DOI
10.1073/pnas.2221929120
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Shin, Jin Young(신진영)
Yoo, Han Soo(유한수) ORCID logo https://orcid.org/0000-0001-7846-6271
Lee, Ji Eun(이지은)
Lee, Phil Hyu(이필휴) ORCID logo https://orcid.org/0000-0001-9931-8462
Chung, Seok Jong(정석종) ORCID logo https://orcid.org/0000-0001-6086-3199
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/198060
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