{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T04:43:31Z","timestamp":1775018611513,"version":"3.50.1"},"reference-count":114,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Abnormal protein accumulations in the brain are linked to aging and the pathogenesis of dementia of various types, including Alzheimer\u2019s disease. These accumulations can be reduced by cell indigenous mechanisms. Among these is autophagy, whereby proteins are transferred to lysosomes for degradation. Autophagic dysfunction hampers the elimination of pathogenic protein aggregations that contribute to cell death. We had observed that the adhesion molecule L1 interacts with microtubule-associated protein 1 light-chain 3 (LC3), which is needed for autophagy substrate selection. L1 increases cell survival in an LC3-dependent manner via its extracellular LC3 interacting region (LIR). L1 also interacts with A\u03b2 and reduces the A\u03b2 plaque load in an AD model mouse. Based on these results, we investigated whether L1 could contribute to autophagy of aggregated A\u03b2 and its clearance. We here show that L1 interacts with autophagy-related protein 12 (ATG12) via its LIR domain, whereas interaction with ubiquitin-binding protein p62\/SQSTM1 does not depend on LIR. A\u03b2, bound to L1, is carried to the autophagosome leading to A\u03b2 elimination. Showing that the mitophagy-related L1-70 fragment is ubiquitinated, we expect that the p62\/SQSTM1 pathway also contributes to A\u03b2 elimination. We propose that enhancing L1 functions may contribute to therapy in humans.<\/jats:p>","DOI":"10.3390\/ijms251910829","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T06:30:03Z","timestamp":1728455403000},"page":"10829","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Functional Relationships between L1CAM, LC3, ATG12, and A\u03b2"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1851-562X","authenticated-orcid":false,"given":"Gabriele","family":"Loers","sequence":"first","affiliation":[{"name":"Zentrum f\u00fcr Molekulare Neurobiologie, Universit\u00e4tsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ute","family":"Bork","sequence":"additional","affiliation":[{"name":"Zentrum f\u00fcr Molekulare Neurobiologie, Universit\u00e4tsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melitta","family":"Schachner","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neuroscience, Keck Center for Collaborative Neuroscience, Rutgers University, 604 Allison Road, Piscataway, NJ 08854, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kozlova, I., Sah, S., Keable, R., Leshchyns\u2019ka, I., Janitz, M., and Sytnyk, V. 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