{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:28:42Z","timestamp":1792700922317,"version":"4.5.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease with progressive loss of motor neurons in the central nervous system. Recent studies have reported that there are mutations at the T-cell antigen-1 (TIA1) domain site in some ALS patients. TIA1 is a key component of stress granules (SGs), but its role and mechanism in ALS pathogenesis remain unclear.<\/jats:p>\n                  <jats:p>In this study, we found that TIA1 was upregulated in the motor cortex of post-mortem ALS patients as well as in the motor cortex neurons of C9orf72-poly-Gly-Ala (GA) mice (ALS mice). TIA1 knockout in the CNS [TIA1Nestin-conditional knockout (CKO) mice] alleviated motor neuron loss, neuroinflammation and motor dysfunction in C9orf72-poly-GA mice. Mechanistically, RNA sequencing combined with the C9orf72-ALS\/frontotemporal dementia patient single nucleus RNA-sequencing database revealed that mRNA of heat shock protein 70 (HSP70) family member genes such as HSPa1b were upregulated in the motor cortex of TIA1Nestin-CKO ALS mice.<\/jats:p>\n                  <jats:p>We further found that TIA1-mediated SG formation was increased during ALS pathogenesis, leading to HSP70 mRNA being sequestered into SGs. This reduced HSP70 expression, impairing the degradation of poly-GA aggregates by the UBQLN2-HSP70 pathway and exacerbating C9orf72-ALS progression.<\/jats:p>\n                  <jats:p>Taken together, these findings highlight a previously unrecognized role of TIA1-mediated SGs in promoting ALS pathogenesis by sequestering HSP70 mRNA, suggesting potential therapeutic targets for ALS treatment.<\/jats:p>","DOI":"10.1093\/brain\/awaf248","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T07:52:01Z","timestamp":1751615521000},"page":"4482-4494","source":"Crossref","is-referenced-by-count":12,"title":["TIA1-mediated stress granules promote neurodegeneration by sequestering\n                    <i>HSP70<\/i>\n                    mRNA in C9orf72 mice"],"prefix":"10.1093","volume":"148","author":[{"given":"Yan","family":"Wei","sequence":"first","affiliation":[{"name":"School of Pharmacy, Hangzhou Normal University , Hangzhou, Zhejiang 311121 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hangzhou Normal University , Hangzhou, Zhejiang 311121 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hangzhou Normal University , Hangzhou, Zhejiang 311121 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanzhu","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hangzhou Normal University , Hangzhou, Zhejiang 311121 ,","place":["China"]},{"name":"Department of Clinical Research Center, Affiliated Hangzhou First People\u2019s Hospital, Westlake University School of Medicine , Hangzhou, Zhejiang 310006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Luo","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hangzhou Normal University , Hangzhou, Zhejiang 311121 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiqiao","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Hangzhou Normal University , Hangzhou, Zhejiang 311121 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hangzhou Normal University , Hangzhou, Zhejiang 311121 ,","place":["China"]},{"name":"Department of Clinical Research Center, Affiliated Hangzhou First People\u2019s Hospital, Westlake University School of Medicine , Hangzhou, Zhejiang 310006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhichao","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hangzhou Normal University , Hangzhou, Zhejiang 311121 ,","place":["China"]},{"name":"Department of Clinical Pharmacy, Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine , Hangzhou, Zhejiang 310016 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyong","family":"Shen","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, School of Medicine, Zhejiang University , Hangzhou, Zhejiang 310020 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Center, Affiliated Hangzhou First People\u2019s Hospital, Westlake University School of Medicine , Hangzhou, Zhejiang 310006 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1927-0946","authenticated-orcid":false,"given":"Zhihui","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Hangzhou Normal University , Hangzhou, Zhejiang 311121 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,7,7]]},"reference":[{"key":"2025120411071223600_awaf248-B1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature20413","article-title":"Decoding ALS: From genes to mechanism","volume":"539","author":"Taylor","year":"2016","journal-title":"Nature"},{"key":"2025120411071223600_awaf248-B2","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.neuron.2020.08.022","article-title":"ALS genetics: Gains, losses, and implications for future 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