Reactive astrocytes acquire neuroprotective as well as deleterious signatures in response to Tau and Aß pathology.

Autor: Jiwaji, Zoeb, Tiwari, Sachin S., Avilés-Reyes, Rolando X., Hooley, Monique, Hampton, David, Torvell, Megan, Johnson, Delinda A., McQueen, Jamie, Baxter, Paul, Sabari-Sankar, Kayalvizhi, Qiu, Jing, He, Xin, Fowler, Jill, Febery, James, Gregory, Jenna, Rose, Jamie, Tulloch, Jane, Loan, Jamie, Story, David, McDade, Karina
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Zdroj: Nature Communications; 1/10/2022, Vol. 13 Issue 1, p1-23, 23p
Abstrakt: Alzheimer's disease (AD) alters astrocytes, but the effect of Aß and Tau pathology is poorly understood. TRAP-seq translatome analysis of astrocytes in APP/PS1 ß-amyloidopathy and MAPTP301S tauopathy mice revealed that only Aß influenced expression of AD risk genes, but both pathologies precociously induced age-dependent changes, and had distinct but overlapping signatures found in human post-mortem AD astrocytes. Both Aß and Tau pathology induced an astrocyte signature involving repression of bioenergetic and translation machinery, and induction of inflammation pathways plus protein degradation/proteostasis genes, the latter enriched in targets of inflammatory mediator Spi1 and stress-activated cytoprotective Nrf2. Astrocyte-specific Nrf2 expression induced a reactive phenotype which recapitulated elements of this proteostasis signature, reduced Aß deposition and phospho-tau accumulation in their respective models, and rescued brain-wide transcriptional deregulation, cellular pathology, neurodegeneration and behavioural/cognitive deficits. Thus, Aß and Tau induce overlapping astrocyte profiles associated with both deleterious and adaptive-protective signals, the latter of which can slow patho-progression. Alzheimer's disease is associated with changes in astrocytes. Here the authors investigated the astrocyte translatome associated with amyloid-ß and tau pathology. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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