Cholesterol impairs autophagy-mediated clearance of amyloid beta while promoting its secretion.

Cholesterol impairs autophagy-mediated clearance of amyloid beta while promoting its secretion. Autophagy. 2018 Jun 04;:1-26 Authors: Barbero-Camps E, Roca-Agujetas V, Bartolessis I, de Dios C, Fernández-Checa JC, Marí M, Morales A, Hartmann T, Colell A Abstract Macroautophagy/autophagy failure with the accumulation of autophagosomes is an early neuropathological feature of Alzheimer disease (AD) that directly affects amyloid beta (Aβ) metabolism. Although loss of presenilin 1 function has been reported to impair lysosomal function and prevent autophagy flux, the detailed mechanism leading to autophagy dysfunction in AD remains to be elucidated. The resemblance between pathological hallmarks of AD and Niemann-Pick Type C disease, including endosome-lysosome abnormalities and impaired autophagy, suggests cholesterol accumulation as a common link. Using a mouse model of AD (APP-PSEN1-SREBF2 mice), expressing chimeric mouse-human amyloid precursor protein with the familial Alzheimer Swedish mutation (APP695swe) and mutant presenilin 1 (PSEN1-dE9), together with a dominant-positive, truncated and active form of SREBF2/SREBP2 (sterol regulatory element binding factor 2), we demonstrated that high brain cholesterol enhanced autophagosome formation, but disrupted its fusion with endosomal-lysosomal vesicles. The combination of these alterations resulted in impaired degradation of Aβ and endogenous MAPT (microtubule associated protein tau...
Source: Autophagy - Category: Cytology Authors: Tags: Autophagy Source Type: research

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Publication date: Available online 17 July 2019Source: Neuroscience LettersAuthor(s): Rehana Khatoon, Md. Zeeshan Rasheed, Mahika Rawat, Mohd. Mumtaz Alam, Heena Tabassum, Suhel ParvezAbstractAlzheimers’s disease is one of the alarming neurodegenerative disease and it is of global concern.The hallmarks of the disease are the amyloid beta (Aβ) aggregation and presence of neurofibrillary tangles (NFTs). The interaction of Aβ with macromolecular targets affects the normal cellular functions. The amyloid peptide interaction with cellular surfaces may trigger the intracellular cascades of signalling. Interaction...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
ConclusionsBased on the population data and our case series, COQ4-related mitochondriopathy is likely an underrecognized condition. We recommend including the COQ4 c.370G > A variant as a part of the screening process for mitochondriopathy in Chinese populations.
Source: Clinica Chimica Acta - Category: Laboratory Medicine Source Type: research
CONCLUSIONS: We highlight the frequent presence of amyloid pathology in prodromal LBD in our population, and the probable involvement of different metabolic pathways in the same clinically defined dementia. PMID: 31309997 [PubMed - in process]
Source: Revista de Neurologia - Category: Neurology Authors: Tags: Rev Neurol Source Type: research
ConclusionsUDCA is a GPBAR1 ligand and exerts beneficial effects in a rodent model of NASH by activating non-overlapping pathway with OCA.
Source: Biochimica et Biophysica Acta (BBA) Molecular and Cell Biology of Lipids - Category: Lipidology Source Type: research
America ’s strong economic growth and high living standards were built on our relatively smaller government. U.S. per capita income is higher than nearly all major countries and our government spending is still somewhat less.However, America ’s lower-spending advantage has diminished. TheOECD publishes data on total federal-state-local government spending as a percentage of GDP for its member countries. The chart shows spending for the United States and for the simple average of 30 OECD countries which have data back to 1995. These are high-income countries such as Canada, Germany, and Japan.The chart shows tha...
Source: Cato-at-liberty - Category: American Health Authors: Source Type: blogs
AbstractBiomarkers classically studied in Alzheimer ’s disease have been analyzed in numerous central nervous system infections in adults, but there are scarce data on these biomarkers in children. Enteroviruses appear to be the most common cause of aseptic meningitis throughout the world. The aim of the study was to investigate neuroinflammatory p roperties of non-polio enteroviruses by measuring CSF concentrations of biomarkers that are involved in neuropathological pathways of neurodegenerative disorders. We measured Aβ42, t-tau, and S100B concentrations in 42 children with enteroviral meningitis (EM) compare...
Source: European Journal of Clinical Microbiology and Infectious Diseases - Category: Microbiology Source Type: research
AbstractStaphylococcus lugdunensis is a coagulase-negative staphylococcus (CoNS) with unusual pathogenicity resembling that ofS. aureus. Unlike other CoNS,S. lugdunensis remains susceptible to most antibiotics. The resistance to penicillin varies widely (range, 15 –87% worldwide), whereas methicillin resistance is still rare. We aimed to evaluate treatment options for infections caused byS. lugdunensis and more specifically to investigate whether penicillin G could be a better treatment choice than oxacillin. Susceptibility testing was performed using the disc diffusion method for penicillin G, cefoxitin, trimethopri...
Source: European Journal of Clinical Microbiology and Infectious Diseases - Category: Microbiology Source Type: research
Conclusions: Our results suggest that professional practices and patient education would benefit from a greater understanding of social and cultural determinants, and that this would also promote patient compliance with instructions regarding physical activity. PMID: 31314680 [PubMed - as supplied by publisher]
Source: Acta Cardiologica - Category: Cardiology Tags: Acta Cardiol Source Type: research
Abstract Drug-induced liver injury (DILI) is an important cause of liver toxicity which can have varying clinical presentations, the most severe of which being acute liver failure. Hepatocyte death as a cause of drug toxicity is a feature of DILI. There are multiple cell death subroutines; some, like apoptosis, necroptosis, autophagy, and necrosis have been extensively studied, while others such as pyroptosis and ferroptosis have been more recently described. The mode of cell death in DILI depends on the culprit drug, as it largely dictates the mechanism and extent of injury. The main cell death subroutines in DIL...
Source: Advances in Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Adv Pharmacol Source Type: research
Publication date: Available online 18 July 2019Source: Molecular Aspects of MedicineAuthor(s): Michael J. Gaudry, Michaela Keuper, Martin JastrochAbstractIn eutherian mammals, brown adipose tissue (BAT) permits non-shivering thermogenesis (NST) through high metabolic rates catalyzed by the unique mitochondrial uncoupling protein 1 (UCP1). The tissue has recently gained remarkable attention due its discovery in adult humans. Approaching BAT and UCP1 as therapeutic targets to combust surplus energy bares high potential to combat the epidemic of the metabolic syndrome that has precipitated in our society as a result of our mo...
Source: Molecular Aspects of Medicine - Category: Molecular Biology Source Type: research
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