{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T01:37:03Z","timestamp":1780105023917,"version":"3.54.0"},"reference-count":28,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,5,18]],"date-time":"2018-05-18T00:00:00Z","timestamp":1526601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>The heat shock response involved in protein misfolding is linked to the formation of toxic immunogenic proteins with heat shock proteins (HSP) as regulators of amyloid beta aggregation. The defective amyloid beta trafficking between different intracellular compartments is now relevant to HSPs and autoimmunity. Overnutrition, temperature dysregulation, and stress repress the heat shock gene Sirtuin 1 with the induction of HSP regulated amyloid beta aggregation involved in the autoimmune response. Defective circadian rhythm alterations are connected to inactivation of the peripheral sink amyloid beta clearance pathway and related to insulin resistance, protein aggregation, and autoimmune disease in non-alcoholic fatty liver disease (NAFLD) and various neurodegenerative diseases such as Alzheimer\u2019s disease. Nutritional therapy is critical to prevent immunosenescence, and plasma Sirtuin 1 levels should be determined to reverse, stabilize, and prevent protein aggregation with relevance to mitochondrial apoptosis and programmed cell death in chronic diseases.<\/jats:p>","DOI":"10.3390\/diseases6020039","type":"journal-article","created":{"date-parts":[[2018,5,21]],"date-time":"2018-05-21T04:07:30Z","timestamp":1526875650000},"page":"39","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Heat Shock Gene Inactivation and Protein Aggregation with Links to Chronic Diseases"],"prefix":"10.3390","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2390-1501","authenticated-orcid":false,"given":"Ian James","family":"Martins","sequence":"first","affiliation":[{"name":"Centre of Excellence in Alzheimer\u2019s Disease Research and Care, Sarich Neuroscience Research Institute, Edith Cowan University, Verdun Street, Nedlands 6009, Australia"},{"name":"School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Nedlands 6009, Australia"},{"name":"McCusker Alzheimer\u2019s Research Foundation, Hollywood Medical Centre, 85 Monash Avenue, Suite 22, Nedlands 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1242\/dmm.014563","article-title":"Barcoding heat shock proteins to human diseases: Looking beyond the heat shock response","volume":"7","author":"Kakkar","year":"2014","journal-title":"Dis. 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