Pathological abnormalities in the tau protein give rise to a variety of neurodegenerative diseases, conjointly termed tauopathies. Several tau mutations have been identified in the tau-encoding gene , affecting either the physical properties of tau or resulting in altered tau splicing. At early disease stages, mitochondrial dysfunction was highlighted with mutant tau compromising almost every aspect of mitochondrial function.
View Article and Find Full Text PDFAbnormal tau protein impairs mitochondrial function, including transport, dynamics, and bioenergetics. Mitochondria interact with the endoplasmic reticulum (ER) via mitochondria-associated ER membranes (MAMs), which coordinate and modulate many cellular functions, including mitochondrial cholesterol metabolism. Here, we show that abnormal tau loosens the association between the ER and mitochondria in vivo and in vitro.
View Article and Find Full Text PDFAbnormal tau protein aggregation in the brain is a hallmark of tauopathies, such as frontotemporal lobar degeneration and Alzheimer's disease. Substantial evidence has been linking tau to neurodegeneration, but the underlying mechanisms have yet to be clearly identified. Mitochondria are paramount organelles in neurons, as they provide the main source of energy (adenosine triphosphate) to these highly energetic cells.
View Article and Find Full Text PDFTreatment with valproate is associated with hepatic steatosis, but the mechanisms are not fully elucidated in human cell systems. We therefore investigated the effects of valproate on fatty acid and triglyceride metabolism in HepaRG cells, a human hepatoma cell line. In previously fatty acid loaded HepaRG cells, valproate impaired lipid droplet disposal starting at 1 mM after incubation for 3 or 7 days.
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