{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:33:34Z","timestamp":1785407614843,"version":"3.56.0"},"reference-count":118,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Postdoctoral Program for Innovative Talent","award":["BX20240155"],"award-info":[{"award-number":["BX20240155"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82401768"],"award-info":[{"award-number":["82401768"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82394421"],"award-info":[{"award-number":["82394421"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82401768"],"award-info":[{"award-number":["82401768"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["82394421"],"award-info":[{"award-number":["82394421"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M761362"],"award-info":[{"award-number":["2024M761362"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2024M761362"],"award-info":[{"award-number":["2024M761362"]}],"id":[{"id":"https:\/\/ror.org\/0426zh255","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","award":["2025JJ90133"],"award-info":[{"award-number":["2025JJ90133"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Leukodystrophies (LDs), a group of heterogeneous genetic disorders, are characterized by selective involvement of cerebral white matter, including abnormal white matter development and\/or progressive degeneration. Oligodendrocytes, astrocytes, microglia, axons, and the neurovascular unit collectively contribute to white matter homeostasis and disease progression. Recently, genomic sequencing has identified pathogenic variants in the alanyl-tRNA synthetase 1 (AARS1) and alanyl-tRNA synthetase 2, mitochondrial (AARS2) genes in LD-related phenotypes. Dysfunction of AARS1 and AARS2 proteins may impair cytosolic or mitochondrial tRNA aminoacylation, compromise editing fidelity, and disrupt mitochondrial homeostasis, which may lead to disruption of protein homeostasis, cellular stress responses, and energy failure. Alanyl-tRNA synthetase (AlaRS) impairments play an important role in the pathological processes of cytosolic and mitochondrial alanyl-tRNA synthetase-related disorders. These molecular defects are associated with characteristic neuroimaging patterns and diverse clinical manifestations observed in AARS1\/AARS2-related disorders. This review summarizes current knowledge on the genetic basis, clinicopathological features, and molecular mechanisms of AARS1- and AARS2-related leukodystrophies, and discusses emerging therapeutic perspectives, with the aim of facilitating precision diagnosis and future targeted interventions.<\/jats:p>","DOI":"10.3390\/genes17080872","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:11:56Z","timestamp":1785168716000},"page":"872","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advances in Research on AARS1\/AARS2-Related Disorders: A Focus on Leukodystrophies"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9081-1869","authenticated-orcid":false,"given":"Zhenyu","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China"},{"name":"Clinical Research Center for Immune-Related Encephalopathy of Hunan Province, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3510-8383","authenticated-orcid":false,"given":"Wendiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China"},{"name":"Clinical Research Center for Immune-Related Encephalopathy of Hunan Province, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengyi","family":"Yu","sequence":"additional","affiliation":[{"name":"Hengyang Medical School, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China"},{"name":"Clinical Research Center for Immune-Related Encephalopathy of Hunan Province, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6636-6000","authenticated-orcid":false,"given":"Miaojin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Hengyang Medical School, University of South China, Hengyang 421001, China"},{"name":"The Key Laboratory of Pediatric Rare Diseases of the Ministry of Education, Hengyang and Central South University, University of South China, Changsha 410078, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beisha","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Multi-Omics Research Center for Brain Disorders, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China"},{"name":"Clinical Research Center for Immune-Related Encephalopathy of Hunan Province, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang 421001, China"},{"name":"Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, China"},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,26]]},"reference":[{"key":"ref_1","first-page":"131","article-title":"Familiar diffuse sclerosis (Leucodystrophia cerebri progressiva hereditaria)","volume":"36","author":"Bielschowsky","year":"1928","journal-title":"J. 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