RAGE-mediated effects of formaldehyde on the course of Alzheimer’s disease

To date, Alzheimer's disease (AD) is an incurable disease with enormous socioeconomic consequences. One of the known mechanisms of Alzheimer's disease pathogenesis is the deposition of amyloid plaques as a result of beta-amyloid (Aβ) accumulation. Receptor for glycation end products (RAGE) plays an important role in the transport of Aβ across the GEB. Also, ligand interaction with RAGE regulates the expression of amyloid precursor protein (APP), which plays a key role in Aβ accumulation. In this analytical review, we dissect the biochemical mechanism of toxic effects of exogenous formaldehyde in the hippocampus leading to the development of insulin resistance and further molecular mechanisms of neuroinflammation contributing to increased RAGE expression. Accumulation of endogenous formaldehyde in the body may occur as a result of impaired utilization. However, the accumulation associated with the ingestion of exogenous formaldehyde has much more acute and dangerous consequences. Formaldehyde is one of the main toxins, MAC of which is stably exceeded in many cities of Russia, as well as in countries of East, South and South-East Asia, Central Africa, North and South America. Formaldehyde plays a major role in the pathogenesis of neurodegenerative diseases, as its biochemical mechanism of action is closely related to increased Aβ accumulation. In individuals more susceptible to beta-amyloid accumulation (due to age or genetic predisposition), exposure to exogenous formaldehyde may have an additional effect on beta-amyloid accumulation. Experiments have previously been conducted investigating the role of formaldehyde in neurodegenerative diseases. A correlation was found between the degree of air pollution and hyperglycaemia. However, the detailed mechanism for the further development of neurodegeneration remains unclear. This review emphasizes the importance of studying the interaction between environmental toxins and neurodegenerative diseases, which may lead to the development of a therapeutic approach based on the protection of neurons from the effects of toxic substances in individuals susceptible to this pathology.