Physical Training Inhibits the Fibrosis Formation in Alzheimer's Disease Kidney Influencing the TGFβ Signaling Pathways

Vince Szegeczki, Helga Perényi, Gabriella Horváth, Barbara Hinnah, Andrea Tamás, Zsolt Radák, Dóra Ábrahám, Róza Zákány, Dóra Reglodi, Tamás Juhász

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Alzheimer's disease (AD) is a neurodegenerative illness, with several peripheral pathological signs such as accumulation of amyloid-β (Aβ) plaques in the kidney. Alterations of transforming growth factor β (TGFβ) signaling in the kidney can induce fibrosis, thus disturbing the elimination of Aβ. Objective: A protective role of increased physical activity has been proven in AD and in kidney fibrosis, but it is not clear whether TGFβ signalization is involved in this effect. Methods: The effects of long-term training on fibrosis were investigated in the kidneys of mice representing a model of AD (B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J) by comparing wild type and AD organs. Alterations of canonical and non-canonical TGFβ signaling pathways were followed with PCR, western blot, and immunohistochemistry. Results: Accumulation of collagen type I and interstitial fibrosis were reduced in kidneys of AD mice after long-term training. AD induced the activation of canonical and non-canonical TGFβ pathways in non-trained mice, while expression levels of signal molecules of both TGFβ pathways became normalized in trained AD mice. Decreased amounts of phosphoproteins with molecular weight corresponding to that of tau and the cleaved C-terminal of AβPP were detected upon exercising, along with a significant increase of PP2A catalytic subunit expression. Conclusion: Our data suggest that physical training has beneficial effects on fibrosis formation in kidneys of AD mice and TGFβ signaling plays a role in this phenomenon.

Original languageEnglish
Pages (from-to)1195-1209
Number of pages15
JournalJournal of Alzheimer's Disease
Volume81
Issue number3
DOIs
Publication statusPublished - 2021
Externally publishedYes

Keywords

  • Alzheimer's disease
  • fibrosis
  • physical activity
  • Smad
  • TGFβ

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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