I. v. administration of 1 M and 2 M NaCl solutions (0.17 ml per 100 g body mass) increased sodium concentration in the blood plasma by 2-5% within 10 min. Hypernatriemia and respective hyperosmia were accompanied by the decrease of the protein level in the blood. The amount of NaCl excretion by kidneys within 1.5 hrs was equal to 18 and 39% of the injected sodium load. Close positive correlation was found between the concentration of osmotically active substances in the blood and reabsorption level of osmotically free water in renal tubules. These data suggest existence of at least two mechanisms for regulation of shifts occurring in disturbances of sodium and osmotic balance: 1) extrarenal factor (physico-chemical-the loss of cell water and/or Na influx into the cell); 2) renal factor--an increase in urine Na excretion and osmotically free water reabsorption.
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Background: The autophagy lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) are key proteostasis mechanisms in cells, which are dysfunctional in AD and linked to protein aggregation and neuronal death. Autophagy is over activated in Alzheimer's disease brain whereas UPS is severely impaired. Activating autophagy has received most attention, however recent evidence suggests that UPS can clear aggregate proteins and a potential therapeutic target for AD and protein misfolding diseases.
View Article and Find Full Text PDFBackground: TREM2 is a lipid-sensing receptor expressed by microglial sub-populations within neuropathological microenvironments, whose downstream signaling promotes microglial survival, plasticity, and migration. Multiple loss-of-function variants strongly implicate TREM2 as a key regulator of Alzheimer's disease (AD) risk. Accordingly, TREM2 antibodies are currently in development to evaluate the therapeutic potential of TREM2 agonism in neurodegenerative diseases.
View Article and Find Full Text PDFBackground: Several studies have shown the influential role of nutraceuticals on cognition and mental functions. Dihydroxytrimethoxyflavone, a natural flavone found in herbal drugs, is documented to be neuroprotective in different model systems. Nevertheless, possible memory improvement effects of dihydroxytrimethoxyflavone via nuclear factor-E2-related factor 2 (Nrf2) (a crucial regulator of antioxidative system) has not been systematically evaluated.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Merry Life Biomedical Company, Ltd., Tainan City, Taiwan, Taiwan.
Background: Alzheimer's disease (AD) is complex in pathogenesis and related to aging biology, especially in late-onset AD. We identified a novel synthetic curcumin analog TML-6 through the platform of 6 biomarkers of anti-aging, anti-inflammation, and anti-Aβ as the potential AD drug candidate. TML-6 exhibits multi-target effects on AD pathogenesis, including the activation of NrF-2, the regulation of autophagic machinery through mTOR, the inhibition of APP synthesis and reduction of Aβ, the upregulation of ApoE, and the inhibition of microglial activation.
View Article and Find Full Text PDFBackground: Memory is influenced by epigenetic mechanisms that regulate gene expression. Histone acetyltransferases (HATs), and histone deacetylases (HDACs), are two competitive enzymes regulating histone acetylation. Histone acetylation is reduced in Alzheimer's disease (AD) brains, and evidence has shown a synergistic regulation of HDACs and HATs activities.
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