{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T18:26:31Z","timestamp":1788373591716,"version":"build-2803163510"},"reference-count":75,"publisher":"The Company of Biologists","issue":"3","license":[{"start":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T00:00:00Z","timestamp":1647820800000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001695","name":"Japan Science and Technology Corporation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001695","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Exercise interventions are beneficial for reducing the risk of age-related diseases, including amyloidosis, but the underlying molecular links remain unclear. Here, we investigated the protective role of interval exercise training in a mouse model of age-related systemic apolipoprotein A-II amyloidosis (AApoAII) and identified potential mechanisms. Mice subjected to 16 weeks of exercise showed improved whole-body physiologic functions and exhibited substantial inhibition of amyloidosis, particularly in the liver and spleen. Exercise activated the hepatic p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway and the downstream transcription factor tumor suppressor p53. This activation resulted in elevated expression and phosphorylation of heat shock protein beta-1 (HSPB1), a chaperone that defends against protein aggregation. In amyloidosis-induced mice, the hepatic p38 MAPK-related adaptive responses were additively enhanced by exercise. We observed that with exercise, greater amounts of phosphorylated HSPB1 accumulated at amyloid deposition areas, which we suspect inhibits amyloid fibril formation. Collectively, our findings demonstrate the exercise-activated specific chaperone prevention of amyloidosis, and suggest that exercise may amplify intracellular stress-related protective adaptation pathways against age-associated disorders, such as amyloidosis.<\/jats:p>","DOI":"10.1242\/dmm.049327","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T10:30:42Z","timestamp":1643625042000},"source":"Crossref","is-referenced-by-count":8,"title":["Exercise suppresses mouse systemic AApoAII amyloidosis through enhancement of the p38 MAPK signaling pathway"],"prefix":"10.1242","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9231-5012","authenticated-orcid":false,"given":"Xiaoran","family":"Cui","sequence":"first","affiliation":[{"name":"Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8016-6649","authenticated-orcid":false,"given":"Jinko","family":"Sawashita","sequence":"additional","affiliation":[{"name":"Products Technology Team, Supplement Strategic Unit, Pharma & Supplemental Nutrition Solutions Vehicle, Kaneka Corporation, Osaka 530-8288, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8097-6756","authenticated-orcid":false,"given":"Jian","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan"},{"name":"Department of Neuro-health Innovation, Institute for Biomedical Sciences, Shinshu University, Matsumoto 390-8621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Aging Biology, Department of Biomedical Engineering, Shinshu University Graduate School of Medicine, Science and Technology, Matsumoto 390-8621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1459-1978","authenticated-orcid":false,"given":"Yuichi","family":"Igarashi","sequence":"additional","affiliation":[{"name":"Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0113-8402","authenticated-orcid":false,"given":"Masayuki","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan"},{"name":"Department of Neuro-health Innovation, Institute for Biomedical Sciences, Shinshu University, Matsumoto 390-8621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0548-9944","authenticated-orcid":false,"given":"Hiroki","family":"Miyahara","sequence":"additional","affiliation":[{"name":"Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, Shinshu University Graduate School of Medicine, Matsumoto 390-8621, Japan"},{"name":"Department of Neuro-health Innovation, Institute for Biomedical Sciences, Shinshu University, Matsumoto 390-8621, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0482-9214","authenticated-orcid":false,"given":"Keiichi","family":"Higuchi","sequence":"additional","affiliation":[{"name":"Department of Neuro-health Innovation, Institute for Biomedical Sciences, Shinshu University, Matsumoto 390-8621, Japan"},{"name":"Community Health Care Research Center, Nagano University Health and Medicine, Nagano 381-2227, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2022,3,21]]},"reference":[{"key":"2022032110434227500_DMM049327C1","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/s40279-013-0127-9","article-title":"The emerging role of p53 in exercise metabolism","volume":"44","author":"Bartlett","year":"2014","journal-title":"Sports Med."},{"key":"2022032110434227500_DMM049327C2","doi-asserted-by":"publisher","first-page":"2687","DOI":"10.1074\/jbc.M117.803411","article-title":"HspB1 and Hsc70 chaperones engage distinct tau species and have different inhibitory effects on amyloid formation","volume":"293","author":"Baughman","year":"2018","journal-title":"J. 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