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

15 hours 53 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.

CD5L promotes phagocytic removal of amyloid beta oligomers and improves cognitive function in a mouse model of Alzheimer's disease

20 hours 10 minutes ago
Alzheimer's disease (AD), a neurodegenerative disorder, is the leading cause of dementia. Amyloid-beta (Aβ) and tau are major contributors to AD onset and progression. Here, we investigate the therapeutic potential of CD5L, a macrophage-specific secretory protein, in reducing Aβ accumulation and improving AD pathology. CD5L directly binds to Aβ, particularly the neurotoxic Aβ42, and blocks their aggregation. Moreover, CD5L enhances microglial phagocytosis against several forms of Aβ40 and Aβ42....
Natsumi Maehara

Action and rest tremor map to distinct networks within the primary motor cortex

20 hours 10 minutes ago
Tremor is a common symptom in movement disorders such as Parkinson disease and essential tremor. While both conditions benefit from deep brain stimulation (DBS), the neural substrates underlying different tremor types and their treatment remain poorly defined. Here, we use DBS network mapping in multiple patient cohorts to investigate whether rest vs. action tremor respond to stimulation of the same or distinct subnetworks within the primary motor cortex. Building on recent functional...
Lukas L Goede

Calcium influx drives m6A-dependent RUNX1T1 splicing to promote adipogenic commitment

20 hours 10 minutes ago
Intermuscular fat infiltration driven by fibro-adipogenic progenitors contributes to the irreversible progression of sarcopenia and reflects a fate shift associated with altered calcium signaling. Using FAP-based adipogenesis models, structural and biochemical analyses, transcriptomic profiling, and in vivo drug exposure studies, we found that Ca^(2+) influx dyshomeostasis promotes adipogenic commitment by triggering calmodulin remodeling, dissociation of the KCNQ1-CaM-FTO complex, nuclear...
Weiqian Jiang

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

20 hours 10 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

20 hours 10 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

20 hours 10 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

20 hours 10 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

20 hours 10 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