Xenobiotics, Trace Metals and Genetics in the Pathogenesis of Tauopathies

Abstract

Tauopathies are a disease group characterized by either pathological accumulation or release of fragments of hyperphosphorylated tau proteins originating from the central nervous system. The tau hypotheses of Parkinson’s and Alzheimer’s diseases contain a clinically diverse spectrum of tauopathies. Studies of case records of various tauopathies may reveal clinical phenotype characteristics of the disease. In addition, improved understanding of different tauopathies would disclose environmental factors, such as xenobiotics and trace metals, that can precipitate or modify the progression of the disorder. Important for diagnostics and monitoring of these disorders is a further development of adequate biomarkers, including refined neuroimaging, or proteomics. Our goal is to provide an in-depth review of the current literature regarding the pathophysiological roles of tau proteins and the pathogenic factors leading to various tauopathies, with the perspective of future advances in potential therapeutic strategies.

Copper, Iron, Selenium and Lipo-Glycemic Dysmetabolism in Alzheimer’s Disease

“…However, dysfunction of the ApoE receptors LRP1 and LRP8 may represent causal factors for the observed microtubule derangement by disrupting the supply of essential nutrients such as cholesterol and selenium. Apparently, tau hyperphosphorylation occurring in AD compromises its normal functions and leads to formation of insoluble neurofibrillary tangles forming bundles of protein filaments [51]. Phosphorylating kinases and de-phosphorylating phosphatases in tandem regulate this process.…”

The Potential Roles of Redox Enzymes in Alzheimer’s Disease: Focus on Thioredoxin

“…APOE4 has the ability to bind β-amyloid and plays a role in Aβ conversion from monomeric and non-toxic forms to oligomers and fibrils (Castano et al., 1995). In addition, numerous studies have demonstrated that exposure to some environmental factors, such as xenobiotics and lifestyle stress, also contribute to the progression of sporadic AD (Aaseth et al., 2020; Madore et al., 2020; Shi et al., 2020).…”