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Immortalized hippocampal astrocytes from 3xTg-AD mice,a new model to study disease-related astrocytic dysfunction:a comparative review

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Neural Regeneration Research 2023年第8期18卷 1672-1678页

作者： Laura Tapella Giulia Dematteis Armando A Genazzani Massimiliano De Paola Dmitry Lim Department of Pharmaceutical Sciences Universitàdel Piemonte Orientale“Amedeo Avogadro”NovaraItaly Department of Neuroscience Mario Negri Institute for Pharmacological Research IRCCSMilanoItaly

Alzheimer's disease(AD)is characterized by complex etiology,long-lasting pathogenesis,and celltype-specific ***,there is no cure for AD,emphasizing the urgent need for a comprehensive understanding of cell-specific ***,principal homeostatic cells of the central nervous system,are key players in the pathogenesis of neurodegenerative diseases,including *** models greatly facilitate the investigation of cell-specific pathological alterations and the dissection of molecular mechanisms and ***-derived and immortalized astrocytic cell lines,alongside the emerging technology of adult induced pluripotent stem cells,are widely used to study cellular dysfunction in ***,no stable cell lines were available from genetic mouse AD ***,we established immortalized hippocampal astroglial cell lines from amyloid-βprecursor protein/presenilin-1/Tau triple-transgenic(3xTg)-AD mice(denominated as wild type(WT)-and 3Tg-iAstro cells)using retrovirus-mediated transduction of simian virus 40 large T-antigen and propagation without clonal selection,thereby maintaining natural heterogeneity of primary *** groups have successfully used 3Tg-iAstro cells for single-cell and omics approaches to study astrocytic AD-related alterations of calcium signaling,mitochondrial dysfunctions,disproteostasis,altered homeostatic and signaling support to neurons,and blood-brain barrier *** we provide a comparative overview of the most used models to study astrocytes in vitro,such as primary culture,tumor-derived cell lines,immortalized astroglial cell lines,and induced pluripotent stem cell-derived *** conclude that immortalized WT-and 3Tg-iAstro cells provide a noncompetitive but complementary,low-cost,easy-to-handle,and versatile cellular model for dissection of astrocyte-specific AD-related alterations and preclinical drug discovery.

关键词： Alzheimer's disease astrocytes immortalization astroglial Alzheimers's disease model blood-brain barrier calcium signaling central nervous system homeostasis disproteostasis endoplasmic reticulum-mitochondria contacts induced pluripotent stem cell-derived astrocytes protein synthesis

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