Abstract
Recent studies have shown that neurodegeneration is closely related to misfolding and aggregation of neuronal tau. Our previous results show that neuronal tau aggregates in formaldehyde solution and that aggregated tau induces apoptosis of SH-SY5Y and hippocampal cells. In the present study, based on atomic force microscopy (AFM) observation, we have found that formaldehyde at low concentrations induces tau polymerization whilst acetaldehyde does not. Neuronal tau misfolds and aggregates into globular-like polymers in 0.01–0.1% formaldehyde solutions. Apart from globular-like aggregation, no fibril-like polymerization was observed when the protein was incubated with formaldehyde for 15 days. SDS-PAGE results also exhibit tau polymerizing in the presence of formaldehyde. Under the same experimental conditions, polymerization of bovine serum albumin (BSA) or α-synuclein was not markedly detected. Kinetic study shows that tau significantly misfolds and polymerizes in 60 minutes in 0.1% formaldehyde solution. However, presence of 10% methanol prevents protein tau from polymerization. This suggests that formaldehyde polymerization is involved in tau aggregation. Such aggregation process is probably linked to the tau's special “worm-like” structure, which leaves the ε-amino groups of Lys and thiol groups of Cys exposed to the exterior. Such a structure can easily bond to formaldehyde molecules in vitro and in vivo. Polymerizing of formaldehyde itself results in aggregation of protein tau. Immunocytochemistry and thioflavin S staining of both endogenous and exogenous tau in the presence of formaldehyde at low concentrations in the cell culture have shown that formaldehyde can induce tau into amyloid-like aggregates in vivo during apoptosis. The significant protein tau aggregation induced by formaldehyde and the severe toxicity of the aggregated tau to neural cells may suggest that toxicity of methanol and formaldehyde ingestion is related to tau misfolding and aggregation.
Highlights
Neuronal tau is an important protein in promoting and stabilizing the microtubule system involved in cellular transport and neuronal morphogenesis
Why did we investigate tau misfolding in the presence of formaldehyde at low concentrations (0.01–0.1%)? Methanol and ethanol are metabolized to formaldehyde and acetaldehyde respectively in our hepatocytes and some neural cells [36,37]
Both formaldehyde and acetaldehyde can go through the blood-brain barrier and cause some lesions to central nervous system (CNS), especially our visual system
Summary
Neuronal tau is an important protein in promoting and stabilizing the microtubule system involved in cellular transport and neuronal morphogenesis. A great deal of evidence has demonstrated that oxidation and glycation stresses are key causal factors of neuronal degenerative diseases [11,12,13] Both of them inevitably produce a variety of unsaturated carbonyls as intermediates, like malondialdehyde and 4-hydroxynonenal, which usually cause carbonyl-amino crosslinking and lead to accumulation of irreversible changes (like lipofuscin) related to various neurodegenerative diseases in particular [14,15,16]. The results showed that low concentrations (0.01–0.1%) of formaldehyde are sufficient to induce formation of amyloid-like tau aggregates, which can induce apoptosis of both SH-SY5Y and hippocampal cells This may be significant to understand the mechanism of chronic damage caused by methanol toxicity and formaldehyde stress [18,28]. The present study concerns the characteristic of misfolding and polymerization of extracellular and intracellular neuronal tau induced by formaldehyde at low concentrations
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
