Kim, Dong Yeol Shin, Jin Young Lee, Ji Eun Kim, Ha Na Chung, Seok Jong Yoo, Han Soo Kim, Sang Jin Cho, Hwa Jin Lee, Eun-Jae Nam, Soo Jeong Kim, Seong Heon Jang, Jaewon Lee, Seung Eun Lee, Phil Hyu 2024-01-12T06:34:00Z 2024-01-12T06:34:00Z 2023-11-22 2023-09 0027-8424 https://pubs.kist.re.kr/handle/201004/79824 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. English National Academy of Sciences A selective ER-phagy exerts neuroprotective effects via modulation of α-synuclein clearance in parkinsonian models Article 10.1073/pnas.2221929120 1 Proceedings of the National Academy of Sciences of the United States of America, v.120, no.37 Proceedings of the National Academy of Sciences of the United States of America 120 37 N scie scopus 001119304600017 Multidisciplinary Sciences Science & Technology - Other Topics Article ENDOPLASMIC-RETICULUM STRESS UNFOLDED PROTEIN RESPONSE AUTOPHAGY CELLS DEGRADATION IDENTIFICATION RESTRICTS TURNOVER Parkinson&apos s disease alpha-synuclein ER-phagy protection FAM134B