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Activation of the heat shock response as a therapeutic strategy for tau toxicity.
Stanley, Taylor R; Otero, Elizabeth M; Knight, Amy L; Saxton, Aleen D; Ding, Xinxing; Borgen, Melissa; Kraemer, Brian C; Kim Guisbert, Karen S; Guisbert, Eric.
Afiliação
  • Stanley TR; Biomedical Sciences Program, Florida Institute of Technology, Melbourne, Florida.
  • Otero EM; Biomedical Sciences Program, Florida Institute of Technology, Melbourne, Florida.
  • Knight AL; Biomedical Sciences Program, Florida Institute of Technology, Melbourne, Florida.
  • Saxton AD; Geriatrics Research Education and Clinical Center (GRECC), Veterans Affairs Puget Sound Healthcare System, 1660 South Columbian Way Seattle, WA 98108-1532, USA.
  • Ding X; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington Harborview Medical Center, 325 9th Ave, Box 359755, Seattle, WA 98104-2499, USA.
  • Borgen M; Department of Psychiatry and Behavioral Sciences, University of Washington, 1959 NE Pacific Street, Box 356560, Seattle, WA 98195-6560, USA.
  • Kraemer BC; Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Box 357470, Seattle, WA 98195, USA.
  • Kim Guisbert KS; Biomedical Sciences Program, Florida Institute of Technology, Melbourne, Florida.
  • Guisbert E; Biomedical Sciences Program, Florida Institute of Technology, Melbourne, Florida.
Dis Model Mech ; 17(9)2024 Sep 01.
Article em En | MEDLINE | ID: mdl-39352120
ABSTRACT
Alzheimer's disease is associated with the misfolding and aggregation of two distinct proteins, beta-amyloid and tau. Previously, it has been shown that activation of the cytoprotective heat shock response (HSR) pathway reduces beta-amyloid toxicity. Here, we show that activation of the HSR is also protective against tau toxicity in a cell-autonomous manner. Overexpression of HSF-1, the master regulator of the HSR, ameliorates the motility defect and increases the lifespan of transgenic C. elegans expressing human tau. By contrast, RNA interference of HSF-1 exacerbates the motility defect and shortens lifespan. Targeting regulators of the HSR also affects tau toxicity. Additionally, two small-molecule activators of the HSR, Geranylgeranylacetone (GGA) and Arimoclomol (AC), have substantial beneficial effects. Taken together, this research expands the therapeutic potential of HSR manipulation to tauopathies and reveals that the HSR can impact both beta-amyloid and tau proteotoxicity in Alzheimer's disease.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas tau / Caenorhabditis elegans / Resposta ao Choque Térmico / Proteínas de Caenorhabditis elegans / Diterpenos Limite: Animals / Humans Idioma: En Revista: Dis Model Mech Assunto da revista: MEDICINA Ano de publicação: 2024 Tipo de documento: Article País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
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XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas tau / Caenorhabditis elegans / Resposta ao Choque Térmico / Proteínas de Caenorhabditis elegans / Diterpenos Limite: Animals / Humans Idioma: En Revista: Dis Model Mech Assunto da revista: MEDICINA Ano de publicação: 2024 Tipo de documento: Article País de publicação: Reino Unido