{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T02:50:54Z","timestamp":1792810254956,"version":"4.5.0"},"reference-count":25,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,3,18]]},"abstract":"<jats:p>The molecular mechanism underlying the selective vulnerability of certain neuronal populations associated with neurodegenerative diseases remains poorly understood. Basal autophagy is important for maintaining axonal homeostasis and preventing neurodegeneration. In this paper, we demonstrate that mice deficient in the metazoan-specific autophagy gene Epg5\/epg-5 exhibit selective damage of cortical layer 5 pyramidal neurons and spinal cord motor neurons. Pathologically, Epg5 knockout mice suffered muscle denervation, myofiber atrophy, late-onset progressive hindquarter paralysis, and dramatically reduced survival, recapitulating key features of amyotrophic lateral sclerosis (ALS). Epg5 deficiency impaired autophagic flux by blocking the maturation of autophagosomes into degradative autolysosomes, leading to accumulation of p62 aggregates and ubiquitin-positive inclusions in neurons and glial cells. Epg5 knockdown also impaired endocytic trafficking. Our study establishes Epg5-deficient mice as a model for investigating the pathogenesis of ALS and indicates that dysfunction of the autophagic\u2013endolysosomal system causes selective damage of neurons associated with neurodegenerative diseases.<\/jats:p>","DOI":"10.1083\/jcb.201211014","type":"journal-article","created":{"date-parts":[[2013,3,12]],"date-time":"2013-03-12T03:59:49Z","timestamp":1363060789000},"page":"731-741","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":131,"title":["Mice deficient in <i>Epg5<\/i> exhibit selective neuronal vulnerability to degeneration"],"prefix":"10.1083","volume":"200","author":[{"given":"Hongyu","family":"Zhao","sequence":"first","affiliation":[{"name":"College of Life Sciences, China Agricultural University, Beijing 100083, China 1"},{"name":"National Institute of Biological Sciences, Beijing 102206, China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan G.","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomacromolecules, Institute of Biophysics 2 ; and 3"},{"name":"State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology; Chinese Academy of Sciences, Beijing 100101, China 2 ; and 3"},{"name":"National Institute of Biological Sciences, Beijing 102206, China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingwei","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomacromolecules, Institute of Biophysics 2 ; and 3"},{"name":"State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology; Chinese Academy of Sciences, Beijing 100101, China 2 ; and 3"},{"name":"National Institute of Biological Sciences, Beijing 102206, China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanjun","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomacromolecules, Institute of Biophysics 2 ; and 3"},{"name":"State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology; Chinese Academy of Sciences, Beijing 100101, China 2 ; and 3"},{"name":"National Institute of Biological Sciences, Beijing 102206, China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Miao","sequence":"additional","affiliation":[{"name":"National Institute of Biological Sciences, Beijing 102206, China 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Du","family":"Feng","sequence":"additional","affiliation":[{"name":"Institute of Neurology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomacromolecules, Institute of Biophysics 2 ; and 3"},{"name":"State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology; Chinese Academy of Sciences, Beijing 100101, China 2 ; and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila L.","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Cell, and Developmental Biology, E\u00f6tv\u00f6s Lor\u00e1nd University, Budapest H-1117, Hungary 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Peking University Third Hospital, Beijing 100191, China 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biomacromolecules, Institute of Biophysics 2 ; and 3"},{"name":"State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology; Chinese Academy of Sciences, Beijing 100101, China 2 ; and 3"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2013,3,11]]},"reference":[{"key":"2023072307071845500_bib1","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.neuron.2006.09.018","article-title":"ALS: a disease of motor neurons and their nonneuronal neighbors","volume":"52","author":"Boill\u00e9e","year":"2006","journal-title":"Neuron."},{"key":"2023072307071845500_bib2","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1016\/j.devcel.2011.08.016","article-title":"Autophagy proteins regulate the secretory component of osteoclastic bone resorption","volume":"21","author":"DeSelm","year":"2011","journal-title":"Dev. 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