The autophagy activator Spermidine reduces neuroinflammation and soluble amyloid beta in an Alzheimer’s disease mouse model
The autophagy activator Spermidine reduces neuroinflammation and soluble amyloid beta in an Alzheimer’s disease mouse model
Abstract Deposition of amyloid beta (Aβ) along with glia cell-mediated neuroinflammation are prominent pathogenic hallmarks of Alzheimer’s disease (AD). In recent years, impairment of autophagy has been found to be another important feature, contributing to AD progression and aging. Therefore, we assessed the effect of the autophagy activator Spermidine, a small body-endogenous polyamine often used as dietary supplement and known to promote longevity, on glia cell-mediated neuroinflammation. Spermidine reduced TLR3- and TLR4- mediated inflammatory processes in microglia and astrocytes by decreasing cytotoxicity, inflammasome activity and NF-κB signaling. In line with these anti-inflammatory effects, oral treatment of the amyloid prone AD-like APPPS1 mice with Spermidine reduced neuroinflammation and neurotoxic soluble Aβ. Mechanistically, single nuclei sequencing revealed microglia as one of the main targets of Spermidine treatment, with increased expression of genes implicated in cell motility and phagocytosis. Thus, Spermidine provides a promising therapeutic potential to target glia cells in AD progression.
Beule Dieter、Heppner Frank L.、Schulz Julia、Hoffmann Christian、Houtman Judith、Sansevrino Roberto、Sigrist Stephan J.、Sterczyk Nele、Braeuning Caroline、Milovanovic Dragomir、Fleck Lara、Conrad Thomas、Freitag Kiara、Obermayer Benedikt、Jendrach Marina
Berlin Institute of Health at Charit¨| ¨C Universit?tsmedizin Berlin, Core Unit BioinformaticsDepartment of Neuropathology, Charit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin, Humboldt-Universit?t zu Berlin, Berlin Institute of Health||German Center for Neurodegenerative Diseases (DZNE) within the Helmholtz Association||Cluster of Excellence, NeuroCureDepartment of Neuropathology, Charit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin, Humboldt-Universit?t zu Berlin, Berlin Institute of HealthLaboratory of Molecular Neuroscience, German Center for Neurodegenerative Diseases (DZNE) within the Helmholtz AssociationDepartment of Neuropathology, Charit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin, Humboldt-Universit?t zu Berlin, Berlin Institute of HealthLaboratory of Molecular Neuroscience, German Center for Neurodegenerative Diseases (DZNE) within the Helmholtz AssociationCluster of Excellence, NeuroCure||Freie Universit?t Berlin, Institute for Biology and Genetics||German Center for Neurodegenerative Diseases (DZNE) within the Helmholtz AssociationDepartment of Neuropathology, Charit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin, Humboldt-Universit?t zu Berlin, Berlin Institute of HealthScientific Genomics Platforms, Max Delbr¨1ck Center for Molecular Medicine (MDC) in the Helmholtz Society Berlin Institute of Health (BIH)Laboratory of Molecular Neuroscience, German Center for Neurodegenerative Diseases (DZNE) within the Helmholtz AssociationDepartment of Neuropathology, Charit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin, Humboldt-Universit?t zu Berlin, Berlin Institute of HealthScientific Genomics Platforms, Max Delbr¨1ck Center for Molecular Medicine (MDC) in the Helmholtz Society Berlin Institute of Health (BIH)Department of Neuropathology, Charit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin, Humboldt-Universit?t zu Berlin, Berlin Institute of Health||German Center for Neurodegenerative Diseases (DZNE) within the Helmholtz AssociationBerlin Institute of Health at Charit¨| ¨C Universit?tsmedizin Berlin, Core Unit BioinformaticsDepartment of Neuropathology, Charit¨| ¨C Universit?tsmedizin Berlin, corporate member of Freie Universit?t Berlin, Humboldt-Universit?t zu Berlin, Berlin Institute of Health
神经病学、精神病学基础医学生物科学研究方法、生物科学研究技术
Alzheimer’s diseaseneuroinflammationmicrogliaastrocytesautophagySpermidinedietary supplementsingle nuclei sequencingphagocytosis
Beule Dieter,Heppner Frank L.,Schulz Julia,Hoffmann Christian,Houtman Judith,Sansevrino Roberto,Sigrist Stephan J.,Sterczyk Nele,Braeuning Caroline,Milovanovic Dragomir,Fleck Lara,Conrad Thomas,Freitag Kiara,Obermayer Benedikt,Jendrach Marina.The autophagy activator Spermidine reduces neuroinflammation and soluble amyloid beta in an Alzheimer’s disease mouse model[EB/OL].(2025-03-28)[2025-07-20].https://www.biorxiv.org/content/10.1101/2021.10.28.466219.点此复制
评论