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P4‐032: Microrna regulation of human brain pericytes
Author(s) -
Aalderink Miranda,
Curtis Maurice A.,
Faull Richard L.M.,
Dragunow Mike
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2015.06.1736
Subject(s) - transfection , microrna , cell growth , biology , human brain , cell , microbiology and biotechnology , cell culture , neuroscience , genetics , gene
subunit (g) that is the regulator for the transport of the enzyme; however it seems to not be essential for enzymatic function. As a transporter for the entry and exit of K and Na respectively, Na, K ATPase regulates the resting and action potentials involved in neurons. It is also necessary for the vectorial transepithelial transportation of certain solutes and can function as a cellular adhesion molecule. Inhibition of Na, K ATPase by ouabain alters localization of TDP-43 and increased tubulin acetylation. The acetylation of tubulin has a regulatory effect on Na, K ATPase function. TDP-43(TAR DNA binding protein 43kda) is a heterogeneous nuclear ribonucleoprotein (hnRNP) that is the major pathological protein in frontotemporal dementia (FTD) and motor neuron disease (MND). Pathologically, TDP-43 forms aggregates in the cytoplasm of neurons. Na+, K+ -ATPase activity is dramatically lower in Alzheimer’s disease brains. This may be due to the toxicity of amyloid beta on Na, K ATPase. Inhibition has also been shown to impair learning and memory. Methods:HEK 293T cells were treated with ouabain (an inhibitor of Na, K ATPase) for 24 and 48 hours. Nuclear/cytoplasmic fractionation, Western blot, immunoprecipatation, immunofluorescence, and viability were performed. Results: When Na, K ATPase is stimulated the amount of acetylated tubulin is reduced therefore the presence of acetylated tubulin occurs when Na, K ATPase is inhibited. It was recently shown that acetylation plays a role in TDP-43 pathology. Conclusions: These results may suggest a role of Na, K ATPase in the pathological accumulation of TDP-43 found inmotor neuron disease, frontotemporal dementia, and Alzheimer’s disease.