Aggregator
Protein traffic jams may explain aging, memory loss, and Alzheimer’s
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.
Hidden driving danger when edible cannabis and alcohol mix
Using cannabis edibles and alcohol together may make drivers far more impaired than either substance alone, according to new research from Johns Hopkins. Even more concerning, common field sobriety tests often failed to detect the cannabis-related impairment.
A silent kidney crisis is spreading far faster than experts expected
A sweeping global study found that chronic kidney disease now affects nearly 800 million people and has become one of the world's leading causes of death. Often silent in its early stages, the condition is also a major contributor to heart disease and may be even more common than current estimates suggest.
CD5L promotes phagocytic removal of amyloid beta oligomers and improves cognitive function in a mouse model of Alzheimer's disease
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....
Action and rest tremor map to distinct networks within the primary motor cortex
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...
Do you want to live forever? Lessons learned from the biology of aging
Aging affects us all, but we still do not know how the process evolves or if we can modulate its pace. This issue of PLOS Biology presents a Collection of articles that explores different aspects of aging, discussing what challenges still need to be overcome.
Calcium influx drives m6A-dependent RUNX1T1 splicing to promote adipogenic commitment
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...
Amyloid precursor protein ortholog Appl acts with Vnd during mushroom body axon growth in Drosophila
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...
Ligand-Independent Activation of Notch1 by Cathepsin L Induces CUX1/p16(INK4a)-Dependent Endothelial Senescence Associated With Atherosclerosis
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...
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
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...
Nuclear accumulation of PANK4 in hippocampal astrocytes aggravates cuproptosis in association with mild cognitive impairment in aged mice
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.
Stereoselective effects of nicotine enantiomers on the gut-brain axis and neuroinflammation in a mouse model of Parkinson's disease
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.
Brazil’s ‘rolling stone reefs’ teem with hidden diversity, DNA reveals
Vast offshore habitats face threats including mining, trawling, and drilling for oil
‘That could be a game changer’: an antiviral pill gets first test for Ebola prevention
Researchers are preparing to launch an unprecedented trial to protect people exposed to Ebola in the DRC and Uganda