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Protein traffic jams may explain aging, memory loss, and Alzheimer’s

8 hours 16 minutes ago
Scientists at Stanford may have uncovered a hidden reason our brains decline with age. Studying the ultra-short-lived turquoise killifish, researchers discovered that the cellular machinery responsible for building proteins begins to jam and malfunction over time. Tiny structures called ribosomes start colliding and stalling while reading genetic instructions, triggering a chain reaction that leads to faulty proteins and harmful clumps linked to diseases like Alzheimer’s.

Amyloid precursor protein ortholog Appl acts with Vnd during mushroom body axon growth in Drosophila

12 hours 34 minutes ago
The amyloid precursor protein (APP) is associated with Alzheimer's disease. Appl is the single Drosophila APP ortholog and is expressed in all neurons throughout development. Appl was previously shown to cell-autonomously modulate axon outgrowth in the mushroom bodies (MBs), the fly olfactory memory center. However, we found that Appld, the only reported null allele, affects the normal function of vnd, the gene just proximal to Appl. To decipher developmental and memory defects specifically due...
Claire Marquilly

Ligand-Independent Activation of Notch1 by Cathepsin L Induces CUX1/p16(INK4a)-Dependent Endothelial Senescence Associated With Atherosclerosis

12 hours 34 minutes ago
Our post-GWAS functional analysis revealed that cathepsin L (CTSL) is an upstream regulator of CUX1, and it induces p16^(INK4a)-dependent and atherosclerosis-associated senescence by indirectly activating CUX1 transcription in a process that requires its proteolytic activity. This suggests an unidentified transcription regulator between CTSL and CUX1, and CTSL-mediated cleavage of this regulator could transcribe CUX1, inducing senescence. Here, in search of this transcriptional regulator, we...
Yuwei Wu

Personalized-Context-Aware Age Gap: A New Multi-Omics Measurement Based on Age-Enhanced Model AOE-Net for Aging Acceleration and Chronic Disease Risk Prediction

12 hours 34 minutes ago
Aging is a global issue that affects human health and increases disease risk. The traditional concept of the "age gap (AG)," defined as the difference between estimated biological age and an individual's chronological age, has been used for self-monitoring the risk of age-related diseases. However, the current AG does not account for the stratified aging patterns across different stages of chronological age, which may lead to biased or paradoxical interpretations of aging acceleration. To...
Feng-Ao Wang

Nuclear accumulation of PANK4 in hippocampal astrocytes aggravates cuproptosis in association with mild cognitive impairment in aged mice

12 hours 34 minutes ago
CONCLUSION: This study identifies a novel pathological mechanism in age-related MCI: the nuclear accumulation of PANK4 in hippocampal exacerbates cuproptosis susceptibility by specifically impairing ATP7B-dependent copper efflux, leading to copper overload. Astrocyte-specific PANK4 ablation mitigates these effects, highlighting PANK4 as a potential therapeutic target for preventing or treating age-associated cognitive decline.
Bo Wang

Stereoselective effects of nicotine enantiomers on the gut-brain axis and neuroinflammation in a mouse model of Parkinson's disease

12 hours 34 minutes ago
INTRODUCTION: Parkinson's disease (PD) is characterized by progressive dopaminergic neurodegeneration, neuroinflammation, and emerging evidence of gut microbiota dysbiosis. Although nicotine has been implicated in neuroprotection, whether its enantiomers exert stereoselective effects on the gut-brain axis remains unknown.
Ruixia Liu