Title:Formaldehyde as a trigger for protein aggregation and potential target for mitigation of age-related, progressive cognitive impairment
Volume: 16
Issue: 5
Author(s): Tao Su, Woodrow C. Monte, Xintian Hu, Yingge He and Rongqiao He
Affiliation:
Keywords:
Aggregation, Alzheimer’s disease, Amyloid β, Aspartame, Formaldehyde (FA), Hyperphosphorylation, Methanol,
Tau protein.
Abstract: Recently, formaldehyde (FA), existing in a number of different cells including neural cells, was found to affect
age-related cognitive impairment. Oral administration of methanol (the metabolic precursor of FA) triggers formation
of senile plaques (SPs) and Tau hyperphosphorylation in the brains of monkeys with memory decline. Intraperitoneal
injection of FA leads to hyperphosphorylation of Tau in wild-type mouse brains and N2a cells through activation
of glycogen synthase kinase-3β (GSK-3β). Furthermore, formaldehyde at low concentrations can directly induce Tau
aggregation and amyloid β (Aβ) peptide deposits in vitro. Formaldehyde-induced Tau aggregation is implicated in cytotoxicity
and neural cell apoptosis. Clarifying how FA triggers Aβ deposits and Tau hyperphosphorlyation will not
only improve our understanding of the molecular and cellular mechanisms of age-related cognitive impairment but will
also contribute to the ongoing investigation of alternate targets for new drugs. Here, we review the role of FA, particularly
that of endogenous origin, in protein aggregation and as a potential drug intervention in the development of agerelated
cognitive impairment.
