{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T18:00:29Z","timestamp":1770055229326,"version":"3.49.0"},"reference-count":117,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\n                    Macroautophagy is essential for the long-term health of neurons and astrocytes in the central nervous system (CNS). The six mammalian ATG8 paralogs (LC3A\/B\/C and GABARAP\/GABARAPL1\/L2) exhibit an emerging \u201cATG8 code\u201d\u2014a division of labor among these proteins that assigns specialized roles in the autophagy pathway to each paralog, enabling fine-tuned proteostasis at synapses and the astrocyte\u2013neuron interface. This review synthesizes how LC3\n                    <jats:italic>versus<\/jats:italic>\n                    GABARAP mediate distinct steps of autophagy (LC3 primarily governs cargo recruitment and phagophore expansion, whereas GABARAP drives autophagosome maturation, transport, and lysosomal fusion) and how these molecular distinctions translate into functional differences in neurons\n                    <jats:italic>versus<\/jats:italic>\n                    astrocytes. Neurons coordinate autophagy across long axons and synapses: presynaptic autophagy clears aging synaptic vesicles and organelles, while postsynaptic autophagy modulates receptor turnover and synaptic plasticity. Astrocytes, by contrast, leverage autophagy for metabolic support and clearance of extracellular debris (e.g., amyloid-\u03b2 plaques), interfacing with neuronal autophagy\n                    <jats:italic>via<\/jats:italic>\n                    transcellular mechanisms. Dysregulation of these processes underlies diverse CNS disorders: impaired autophagic flux and aggregate clearance contribute to neurodegenerative diseases (Alzheimer\u2019s and Parkinson\u2019s), whereas selective autophagy deficits at synapses disrupt circuit homeostasis (implicated in epilepsy and autism). Finally, we highlight emerging methodologies\u2014from multi-omics and live imaging to optogenetics and targeted therapeutics\u2014that are illuminating this specialized autophagy network and opening novel avenues for intervention.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2026.1762891","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T06:31:29Z","timestamp":1770013889000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Decoding the brain\u2019s ATG8 paralog code: LC3\u2013GABARAP specialization at synapses and the astrocyte\u2013neuron interface"],"prefix":"10.3389","volume":"14","author":[{"given":"Haneul","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Biological Sciences and Biotechnology, College of Life Sciences and Nanotechnology, Hannam University","place":["Daejeon, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung-Min","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Biotechnology, College of Life Sciences and Nanotechnology, Hannam University","place":["Daejeon, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-A.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and Biotechnology, College of Life Sciences and Nanotechnology, Hannam University","place":["Daejeon, Republic of Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1093\/brain\/awac068","article-title":"Reactive astrocytes promote proteostasis in Huntington\u2019s disease through the JAK2-STAT3 pathway","volume":"146","author":"Abjean","year":"2023","journal-title":"Brain"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1863","DOI":"10.1080\/15548627.2025.2506292","article-title":"Epilepsy and autophagy modulators: a therapeutic split","volume":"21","author":"Al-Kuraishy","year":"2025","journal-title":"Autophagy"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/cells9112413","article-title":"Amyotrophic lateral sclerosis and autophagy: dysfunction and therapeutic targeting","volume":"9","author":"Amin","year":"2020","journal-title":"Cells"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1016\/j.neuron.2023.02.001","article-title":"EndophilinA-dependent coupling between activity-induced calcium influx and synaptic autophagy is disrupted by a Parkinson-risk mutation","volume":"111","author":"Bademosi","year":"2023","journal-title":"Neuron"},{"key":"B5","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1038\/nchembio.1563","article-title":"Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models","volume":"10","author":"Barmada","year":"2014","journal-title":"Nat. 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