{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:50:11Z","timestamp":1790776211153,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["81801241"],"award-info":[{"award-number":["81801241"]}]},{"name":"National Natural Science Foundation of China","award":["81873563"],"award-info":[{"award-number":["81873563"]}]},{"name":"National Natural Science Foundation of China","award":["2019LZXNYDZ05"],"award-info":[{"award-number":["2019LZXNYDZ05"]}]},{"name":"National Natural Science Foundation of China","award":["202010632076"],"award-info":[{"award-number":["202010632076"]}]},{"name":"Collaborative Fund of Science and Technology Agency of Luzhou Government and Southwest Medical University","award":["81801241"],"award-info":[{"award-number":["81801241"]}]},{"name":"Collaborative Fund of Science and Technology Agency of Luzhou Government and Southwest Medical University","award":["81873563"],"award-info":[{"award-number":["81873563"]}]},{"name":"Collaborative Fund of Science and Technology Agency of Luzhou Government and Southwest Medical University","award":["2019LZXNYDZ05"],"award-info":[{"award-number":["2019LZXNYDZ05"]}]},{"name":"Collaborative Fund of Science and Technology Agency of Luzhou Government and Southwest Medical University","award":["202010632076"],"award-info":[{"award-number":["202010632076"]}]},{"name":"National College Students\u2019 innovation and entrepreneurship training program","award":["81801241"],"award-info":[{"award-number":["81801241"]}]},{"name":"National College Students\u2019 innovation and entrepreneurship training program","award":["81873563"],"award-info":[{"award-number":["81873563"]}]},{"name":"National College Students\u2019 innovation and entrepreneurship training program","award":["2019LZXNYDZ05"],"award-info":[{"award-number":["2019LZXNYDZ05"]}]},{"name":"National College Students\u2019 innovation and entrepreneurship training program","award":["202010632076"],"award-info":[{"award-number":["202010632076"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Charcot-Marie-Tooth (CMT) disease is the most common inherited neurodegenerative disorder with selective degeneration of peripheral nerves. Despite advances in identifying CMT-causing genes, the underlying molecular mechanism, particularly of selective degeneration of peripheral neurons remains to be elucidated. Since peripheral neurons are sensitive to multiple stresses, we hypothesized that daily repeated stress might be an essential contributor to the selective degeneration of peripheral neurons induced by CMT-causing mutations. Here, we mainly focused on the biological effects of the dominant missense mutation (S135F) in the 27-kDa small heat-shock protein HSPB1 under repeated heat shock. HSPB1S135F presented hyperactive binding to both \u03b1-tubulin and acetylated \u03b1-tubulin during repeated heat shock when compared with the wild type. The aberrant interactions with tubulin prevented microtubule-based transport of heat shock-induced misfolded proteins for the formation of perinuclear aggresomes. Furthermore, the transport of autophagosomes along microtubules was also blocked. These results indicate that the autophagy pathway was disrupted, leading to an accumulation of ubiquitinated protein aggregates and a significant decrease in cell adaptation to repeated stress. Our findings provide novel insights into the molecular mechanisms of HSPB1S135F-induced selective degeneration of peripheral neurons and perspectives for targeting autophagy as a promising therapeutic strategy for CMT neuropathy.<\/jats:p>","DOI":"10.3390\/cells11182886","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T22:11:10Z","timestamp":1663279870000},"page":"2886","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Charcot-Marie-Tooth-Causing Mutation in HSPB1 Decreases Cell Adaptation to Repeated Stress by Disrupting Autophagic Clearance of Misfolded Proteins"],"prefix":"10.3390","volume":"11","author":[{"given":"Xuelian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medical Science, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaru","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medical Science, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronglin","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medical Science, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Medicine Chemistry, School of Pharmacy, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medical Science, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medical Science, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5909-2892","authenticated-orcid":false,"given":"Ying","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medical Science, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9898-4607","authenticated-orcid":false,"given":"Wei","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering, School of Life Sciences, Zhongshan Hospital, Fudan University, Shanghai 200438, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1269-683X","authenticated-orcid":false,"given":"Xianchao","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Medicine Chemistry, School of Pharmacy, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, School of Basic Medical Science, Southwest Medical University, Luzhou 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0092-8674(91)90613-4","article-title":"DNA Duplication Associated with Charcot-Marie-Tooth Disease Type-1a","volume":"66","author":"Lupski","year":"1991","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pyromali, I., Benslimane, N., Favreau, F., Goizet, C., Lazaro, L., Vitry, M., Derouault, P., Sturtz, F., Magdelaine, C., and Lia, A.S. 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