PT  - JOURNAL ARTICLE
AU  - Kiara Freitag
AU  - Nele Sterczyk
AU  - Julia Schulz
AU  - Judith Houtman
AU  - Lara Fleck
AU  - Stephan J. Sigrist
AU  - Frank L. Heppner
AU  - Marina Jendrach
TI  - The autophagy activator Spermidine ameliorates Alzheimer’s disease pathology and neuroinflammation in mice
AID  - 10.1101/2020.12.27.424477
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.12.27.424477
4099  - http://biorxiv.org/content/early/2020/12/28/2020.12.27.424477.short
4100  - http://biorxiv.org/content/early/2020/12/28/2020.12.27.424477.full
AB  - Deposition of amyloid beta (Aβ) and phosphorylated Tau along with microglia- and astrocyte-mediated neuroinflammation are prominent pathogeneic features of Alzheimer’s Disease (AD). In recent years, impairment of autophagy has also been shown to contribute to AD progression. Here, we provide evidence that oral treatment of amyloid-prone AD-like APPPS1 mice with the autophagy activator Spermidine, a small body-endogenous polyamine often used as dietary supplement, decreased neuroinflammation and reduced neurotoxic soluble Aβ at both early and late stages of AD. Mechanistically, Spermidine induced autophagy in microglia as well as in astrocytes, which subsequently impacted TLR3- and TLR4-mediated inflammatory processes by decreasing cytotoxicity, inflammasome activity and NF-κB signalling. Our data highlight that autophagy targets the inflammatory response of glial cells and emphasize the potential of orally administered autophagy-activating drugs such as Spermidine to interfere with AD progression.Competing Interest StatementThe authors have declared no competing interest.