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Scientists are raising new questions about vitamin B12 and cancer

2 weeks ago
Vitamin B12 has long been seen as a health hero, helping the body make red blood cells, repair DNA, and keep nerves functioning properly. But scientists are discovering that the story may be more complicated than simply “more is better.” While too little B12 can damage DNA and raise cancer risk, some studies suggest that extremely high levels — especially from long-term high-dose supplements — may also be linked to certain cancers or poorer outcomes in cancer patients.

Scientists create supercharged vitamin K that helps the brain heal itself

2 weeks ago
Scientists in Japan have created powerful new vitamin K-based compounds that may help the brain regenerate lost neurons — a breakthrough that could one day change how diseases like Alzheimer’s and Parkinson’s are treated. By combining vitamin K with components related to vitamin A, the researchers developed compounds that were about three times more effective at turning neural stem cells into neurons than natural vitamin K alone.

Revisiting butyrylcholinesterase in Alzheimer's disease: A hub linking cholinergic, metabolic and affective pathways

2 weeks 1 day ago
Selective butyrylcholinesterase (BChE) inhibition is gaining renewed attention as a potential therapeutic strategy for Alzheimer's disease (AD), particularly in advanced stages marked by a shift from acetylcholinesterase (AChE) to BChE dominance. Beyond cholinergic regulation, BChE participates in metabolic, inflammatory, and affective pathways, including the enzymatic control of acyl ghrelin that influences appetite, energy balance, and mood. Preclinical and experimental evidence suggests that...
Barbora Svobodova

Targeting tau-mitochondrial crosstalk in Alzheimer's disease with an Integrative multi-omics and artificial intelligence driven tools for the development of disease-modifying therapeutics

2 weeks 1 day ago
Alzheimer's disease (AD) is a progressive neurodegenerative illness marked by cognitive impairment, synaptic dysfunction and neuronal death. Tau protein abnormalities and mitochondrial dysfunction are key features of its pathogenesis, and both are involved in driving disease development. Emerging evidence suggests that pathogenic tau not only destabilizes microtubules but also directly compromises mitochondrial dynamics, bioenergetics and quality control, ultimately aggravating...
Shanmugam Bhasha

Transmembrane domain switching controls PINK1 import and fate in mitochondria

2 weeks 1 day ago
Mitochondrial targeting of the PINK1 kinase results, under normal conditions, in membrane-potential-driven inner membrane penetration and cleavage by the resident protease PARL before retro-translocation and proteasomal degradation. In compromised mitochondria, with reduced membrane potential, inner membrane incorporation is not achieved, which leads to surface activation of the full-length protein, Parkin recruitment and mitophagy. Here, we identify a third pathway in which PINK1 is imported...
James S Lorriman

FAM134B-mediated ER-phagy degrades APP and suppresses Alzheimer's disease pathology

2 weeks 1 day ago
Endoplasmic reticulum autophagy (ER-phagy) is a selective autophagy pathway in which receptor proteins target ER membranes and proteins for degradation, yet its role in Alzheimer's disease (AD) remains unclear. Here, we identify FAM134B/RETREG1 as a specific ER-phagy receptor mediating amyloid precursor protein (APP) degradation. FAM134B directly interacts with ER-localized wild-type and familial mutant APP via their C-terminal domains and recruits LC3 through its LC3-interacting region (LIR) to...
Yuting Zhang

Microglial mitochondria transfer to astrocytes via GPNMB-enriched extracellular vesicles alleviates cognitive deficits in tauopathy mice

2 weeks 1 day ago
Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by cognitive decline. The precise molecular mechanisms that underlie the pathogenesis of AD remain elusive. Here we show that glycoprotein nonmetastatic melanoma protein B (GPNMB) is produced by microglia and transferred to astrocytes through extracellular vesicles (EVs) in PS19 tau pathology mice. Tau is cleaved in microglia to generate N-terminal fragments that form a complex on mitochondria with Parkin/Nix and...
Chensi Liang

TPPP/p25 amyloid seeding activity as a specific biomarker for multiple system atrophy

2 weeks 1 day ago
Detection of α-synuclein (α-syn) amyloid seeds in human biofluids has attracted great interest for clinical diagnosis of synucleinopathies. However, as a common biomarker, α-syn lacks specificity in reliably differentiating distinct disorders. Here, we report tubulin polymerization promoting protein (TPPP/p25) as a cerebrospinal fluid (CSF) biomarker for the specific diagnosis of multiple system atrophy (MSA). We demonstrate that native TPPP/p25 is self-protected against amyloid aggregation,...
Shuyi Zeng

Host-microbial interactions at the nasal mucosa in young children and adults: A retrospective, cross-sectional study

2 weeks 1 day ago
Young children are at increased risk for respiratory tract infections and are frequently colonized by respiratory pathogens. However, how the mucosal immune system differs between children and adults is relatively unknown. We collected nasal samples from 50 young children (aged 1-5 years) and 318 young adults (aged 18-34 years) to study how the mucosal immune system and host-microbe interactions differ with age. We used multi-omics data integration to combine host (immunophenotyping,...
Jesús Reiné

Remembrance of things past: Towards a life-course biology of aging

2 weeks 1 day ago
Globally, the growing proportion of older individuals is imposing personal and societal costs. However, interventions that slow aging are possible; for example, dampened nutrient signaling pathway activity in animal models promotes better health later in life. Recent findings indicate that such interventions have long-term effects even when applied transiently in early adulthood, forming a "physiological memory." Similar memory has been extensively documented in human epidemiology, where the...
Sara Alam