Amyloid-like aggregates of neuronal tau induced by formaldehyde promote apoptosis of neuronal cells.
BACKGROUND
The microtubule associated protein tau is the principle component of neurofibrillar tangles, which are a characteristic marker in the pathology of Alzheimer's disease; similar lesions are also observed after chronic alcohol abuse. Formaldehyde is a common environmental contaminant and also a metabolite of methanol. Although many studies have been done on methanol and formaldehyde intoxication, none of these address the contribution of protein misfolding to the pathological mechanism, in particular the effect of formaldehyde on protein conformation and polymerization.


RESULTS
We found that unlike the typical globular protein BSA, the natively-unfolded structure of human neuronal tau was induced to misfold and aggregate in the presence of ~0.01% formaldehyde, leading to formation of amyloid-like deposits that appeared as densely staining granules by electron microscopy and atomic force microscopy, and bound the amyloid-specific dyes thioflavin T and Congo Red. The amyloid-like aggregates of tau were found to induce apoptosis in the neurotypic cell line SH-SY5Y and in rat hippocampal cells, as observed by Hoechst 33258 staining, assay of caspase-3 activity, and flow cytometry using Annexin V and Propidium Iodide staining. Further experiments showed that Congo Red specifically attenuated the caspase-3 activity induced by amyloid-like deposits of tau.


CONCLUSIONS
The results suggest that low concentrations of formaldehyde can induce human tau protein to form neurotoxic aggregates, which could play a role in the induction of tauopathies.
Nie
Chun Lai
CL
State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, 15 Datun Rd, Chaoyang District, Beijing 100101, China. niecl1022@ioz.ac.cn <niecl1022@ioz.ac.cn>
Wang
Xing Sheng
XS
Liu
Ying
Y
Perrett
Sarah
S
He
Rong Qiao
RQ
D000682:Amyloid / Q000378:metabolism* / Q000648:ultrastructure*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde / Q000008:administration & dosage*; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism* / Q000648:ultrastructure; D016875:tau Proteins / Q000378:metabolism* / Q000648:ultrastructure*
D000682:Amyloid; D016875:tau Proteins; D005557:Formaldehyde