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Clonal tracing with somatic epimutations reveals dynamics of blood ageing
A retrograde planet in a tight binary star system with a white dwarf
Unravelling cysteine-deficiency-associated rapid weight loss
These malaria drugs treat the mosquitoes — not the people
AI linked to explosion of low-quality biomedical research papers
Before studying parasites, this PhD researcher was their host
The Age of Reason
#OpenToWork: how laid-off US scientists are coping with shattered careers
Are groundbreaking science discoveries becoming harder to find?
Bird feeders have caused a dramatic evolution of California hummingbirds
Beaks have grown longer and larger, and ranges have expanded to follow the feeders
Lotions and perfume can weaken a ‘human oxidation field’ made by your skin
Personal care products may chemically alter the air around us. Whether that’s good or bad remains unclear
Crippling tropical diseases threaten to surge after U.S. funding cuts
Closing of programs that fought neglected diseases imperils drug donation and distribution efforts in 26 countries
Amyloid-beta induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer's disease
Microglial phagocytosis genes have been linked to increased risk for Alzheimer's disease (AD), but the mechanisms translating genetic association to cellular dysfunction remain unknown. Here, we showed that microglia formed lipid droplets (LDs) upon amyloid-β (Aβ) exposure and that LD loads increased with proximity to amyloid plaques in brains from individuals with AD and the 5xFAD mouse model. LD-laden microglia exhibited defects in Aβ phagocytosis, and unbiased lipidomic analyses identified a...
Chromogranin A deficiency attenuates tauopathy by altering epinephrine-alpha-adrenergic receptor signaling in PS19 mice
Metabolic disorders such as insulin resistance and hypertension are potential risk factors for aging and neurodegenerative diseases. These conditions are reversed in Chromogranin A (CgA) knockout (CgA-KO) mice. CgA is known to be associated with protein aggregates in the brains of neurodegenerative diseases including Alzheimer's disease (AD). Here, we investigated the role of CgA in Tau pathogenesis in AD and corticobasal degeneration (CBD). CgA ablation in Tauopathy mice (PS19) (CgA-KO/PS19)...
An integrative systems-biology approach defines mechanisms of Alzheimer's disease neurodegeneration
Despite years of intense investigation, the mechanisms underlying neuronal death in Alzheimer's disease, remain incompletely understood. To define relevant pathways, we conducted an unbiased, genome-scale forward genetic screen for age-associated neurodegeneration in Drosophila. We also measured proteomics, phosphoproteomics, and metabolomics in Drosophila models of Alzheimer's disease and identified Alzheimer's genetic variants that modify gene expression in disease-vulnerable neurons in...
Human mitochondrial ferritin exhibits highly unusual iron-O<sub>2</sub> chemistry distinct from that of cytosolic ferritins
Ferritins are ubiquitous proteins that function in iron storage/detoxification by catalyzing the oxidation of Fe^(2+) ions and solubilizing the resulting Fe^(3+)-oxo mineral. Mammalian tissues that are metabolically highly active contain, in addition to the widespread cytosolic ferritin, a ferritin that is localized to mitochondria. Mitochondrial ferritin (FtMt) protects against oxidative stress and is found at higher levels in diseases associated with abnormal iron accumulation, including...
Large-scale plasma proteomic profiling unveils diagnostic biomarkers and pathways for Alzheimer's disease
Proteomic studies have been instrumental in identifying brain, cerebrospinal fluid and plasma proteins associated with Alzheimer's disease (AD). Here, we comprehensively examined 6,905 aptamers corresponding to 6,106 unique proteins in plasma in more than 3,300 well-characterized individuals to identify new proteins, pathways and predictive models for AD. We identified 416 proteins (294 new) associated with clinical AD status and validated the findings in two external datasets representing more...
Activation of AMPK by GLP-1R agonists mitigates Alzheimer-related phenotypes in transgenic mice
Individuals with type 2 diabetes mellitus have an increased risk of developing Alzheimer's disease (AD). GLP-1 receptor agonists (GLP-1RAs) are used for glycemic control in diabetes and show potential neuroprotective properties, but their effects on AD and the underlying mechanisms are not well understood. Here we demonstrate that GLP-1RAs can alleviate AD-related phenotypes by activating 5' AMP-activated protein kinase (AMPK) signaling. We found that plasma GLP-1 levels were decreased in AD...
GLP-1R agonists protect against Alzheimer's disease by rewiring energy regulation
No abstract
Chromogranin A deficiency attenuates tauopathy by altering epinephrine-alpha-adrenergic receptor signaling in PS19 mice
Metabolic disorders such as insulin resistance and hypertension are potential risk factors for aging and neurodegenerative diseases. These conditions are reversed in Chromogranin A (CgA) knockout (CgA-KO) mice. CgA is known to be associated with protein aggregates in the brains of neurodegenerative diseases including Alzheimer's disease (AD). Here, we investigated the role of CgA in Tau pathogenesis in AD and corticobasal degeneration (CBD). CgA ablation in Tauopathy mice (PS19) (CgA-KO/PS19)...