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Human and mouse proteomics reveals the shared pathways in Alzheimer's disease and delayed protein turnover in the amyloidome

10 months 2 weeks ago
Murine models of Alzheimer's disease (AD) are crucial for elucidating disease mechanisms but have limitations in fully representing AD molecular complexities. Here we present the comprehensive, age-dependent brain proteome and phosphoproteome across multiple mouse models of amyloidosis. We identified shared pathways by integrating with human metadata and prioritized components by multi-omics analysis. Collectively, two commonly used models (5xFAD and APP-KI) replicate 30% of the human protein...
Jay M Yarbro

Unraveling AURKB as a potential therapeutic target in pulmonary hypertension using integrated transcriptomic analysis and pre-clinical studies

10 months 2 weeks ago
Despite advances in treatment, the prognosis for patients with pulmonary arterial hypertension (PAH) remains dismal, highlighting the need for further therapeutic advances. By using RNA sequencing on pulmonary artery smooth muscle cells (PASMCs), functional enrichment, and connectivity map analyses, we identify Aurora kinase B (AURKB) as a candidate therapeutic target. We show that AURKB inhibition blocks cell cycle progression and reverses the gene signature of PAH-PASMCs. We also report that...
Sarah-Eve Lemay

Impact of physical activity on physical function, mitochondrial energetics, ROS production, and Ca(2+) handling across the adult lifespan in men

10 months 2 weeks ago
Aging-related muscle atrophy and weakness contribute to loss of mobility, falls, and disability. Mitochondrial dysfunction is widely considered a key contributing mechanism to muscle aging. However, mounting evidence positions physical activity as a confounding factor, making unclear whether muscle mitochondria accumulate bona fide defects with aging. To disentangle aging from physical activity-related mitochondrial adaptations, we functionally profiled skeletal muscle mitochondria in 51...
Marina Cefis

Rpl12 is a conserved ribophagy receptor

10 months 2 weeks ago
Ribophagy is a selective autophagic process that regulates ribosome turnover. Although NUFIP1 has been identified as a mammalian receptor for ribophagy, its homologues do not exist in yeast and nematodes. Here we demonstrate that Rpl12, a ribosomal large subunit protein, functions as a conserved ribophagy receptor in multiple organisms. Disruption of Rpl12-Atg8s binding leads to significant accumulation of ribosomal proteins and rRNA, while Atg1-mediated Rpl12 phosphorylation enhances its...
Yuting Chen