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  • Formaldehyde induces hyperphosphorylation and polymerization of Tau protein both in vitro and in vivo.

Formaldehyde induces hyperphosphorylation and polymerization of Tau protein both in vitro and in vivo.

Biochimica et biophysica acta (2013-05-01)
Jing Lu, Junye Miao, Tao Su, Ying Liu, Rongqiao He
초록

Chronic formaldehyde exposure leads to memory impairment and abnormal elevation of endogenous formaldehyde has been found in the brains of Alzheimer's disease (AD) patients. Hyperphosphorylated Tau protein with subsequent aggregates as neurofibrillary tangles (NFTs) is one of the typical pathological characteristics in AD brains. The mechanism underlying abnormally elevated concentrations of endogenous formaldehyde that induce Tau hyperphosphorylation is unknown. N2a cells and mice were treated with formaldehyde for different time points, then Western blotting and immunocytochemistry were utilized to determine the phosphorylation and polymerization of Tau protein. HPLC was used to detect the concentration of formaldehyde in cell media. Under formaldehyde stress, Tau became hyperphosphorylated, not only in the cytoplasm, but also in the nucleus of neuroblastoma (N2a) cells, and mouse brains. Polymers of cellular phospho-Tau were also detected. Significant accumulation of glycogen synthase kinase-3β (GSK-3β) in the nucleus of N2a and mouse brain cells, and elevation of its phosphorylation at Y216, was observed under formaldehyde stress. Formaldehyde-induced Tau hyperphosphorylation was blocked in the presence of LiCl and CT99021, inhibitors of GSK-3β, and by RNAi interference. Formaldehyde, which may cause age-related memory loss, can act as a factor triggering Tau hyperphosphorylation via GSK-3β catalysis and induces polymerization of Tau. Investigation of formaldehyde-induced Tau hyperphosphorylation may provide novel insights into mechanisms underlying tauopathies.

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Sigma-Aldrich
Formaldehyde solution, for molecular biology, BioReagent, ≥36.0% in H2O (T)
Supelco
Formaldehyde solution, stabilized with methanol, ~37 wt. % in H2O, certified reference material
Sigma-Aldrich
Formaldehyde solution, meets analytical specification of USP, ≥34.5 wt. %
Sigma-Aldrich
Formaldehyde solution, for molecular biology, 36.5-38% in H2O
SAFC
Formaldehyde solution, contains 10-15% methanol as stabilizer, 37 wt. % in H2O
Sigma-Aldrich
Formaldehyde solution, ACS reagent, 37 wt. % in H2O, contains 10-15% Methanol as stabilizer (to prevent polymerization)
Sigma-Aldrich
Formaldehyde solution, tested according to Ph. Eur.