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NLRP3-mediated glutaminolysis controls microglial phagocytosis to promote Alzheimer's disease progression

4 months ago
Activation of the NLRP3 inflammasome has been implicated in the pathogenesis of Alzheimer's disease (AD) via the release of IL-1β and ASC specks. However, whether NLRP3 is involved in pathways beyond this remained unknown. Here, we found that Aβ deposition in vivo directly triggered NLRP3 activation in APP/PS1 mice, which model many features of AD. Loss of NLRP3 increased glutamine- and glutamate-related metabolism and increased expression of microglial Slc1a3, which was associated with enhanced...
Róisín M McManus

Autophagy-dependent changes in alternative splicing bias translation toward inflammation in senescent cells

4 months ago
Despite limited translational capacity, senescent cells trigger inflammation by upregulating the translation and secretion of proinflammatory factors. In this issue of Developmental Cell, Kim et al. identify that altered autophagy and SFPQ-dependent EIF4H splicing during senescence redirects translation to promote inflammation, informing therapeutic strategies for cancer and other age-related diseases.
Anson Ming Yan Lee

Impact of APOE, Klotho, and sex on cognitive decline with aging

4 months ago
The effects of apolipoprotein E (APOE) and Klotho genes, both implicated in aging, on human cognition as a function of sex and age are yet to be definitively established. Here, we showed in the largest cohort studied to date (N = 320,861) that APOE homozygous ε4 carriers had a greater decline in cognition with aging compared to ε3 carriers (ε3/ε4 and ε3/ε3) as well as smaller hippocampi and amygdala (N = 29,510). Critically, sex and age differentially affected the decline in cognition. Younger...
Kengo Shibata

<em>Octodon degus</em> laboratory colony management principles and methods for behavioral analysis for Alzheimer's disease neuroscience research

4 months ago
The Chilean degu (Octodon degus) is a medium sized, long-lived rodent with traits that make them a natural model for neuroscience research. Their social behaviors, diurnality, and extended developmental time course, when compared to other rodents, make them useful for social behavioral, chronobiology, and developmental research. Lab-kept degus have a long lifespan (5-8 years) and may naturally develop age-related diseases that resemble Alzheimer's disease. While there is significant interest in...
B Maximiliano Garduño

Nicotinamide Riboside Supplementation Alleviates Testicular Aging Induced by Disruption of Qprt-Dependent NAD(+) De Novo Synthesis in Mice

4 months ago
Recent studies have shown that disruptions in the nicotinamide adenine dinucleotide (NAD^(+)) de novo synthesis pathway accelerate ovarian aging, yet its role in spermatogenesis remains largely unknown. In this study, we investigated the impact of the NAD^(+) de novo synthesis pathway on spermatogenesis by generating Qprt-deficient mice using CRISPR-Cas9 to target quinolinate phosphoribosyl transferase (Qprt), a key enzyme predominantly expressed in spermatocytes. Our results revealed that the...
Yining Xu