Homocysteine Thiolactone Detoxifying Enzymes and Alzheimer’s Disease
Abstract
Elevated levels of homocysteine (Hcy) and related metabolites are associated with Alzheimer’s disease (AD). Severe hyperhomocysteinemia causes neurological deficits and worsens behavioral and biochemical traits associated with AD. Although Hcy is precluded from entering the Genetic Code by proofreading mechanisms of aminoacyl-tRNA synthetases, and thus is a non-protein amino acid, it can be attached to proteins via an N-homocysteinylation reaction mediated by Hcy-thiolactone. Because N-homocysteinylation is detrimental to a protein’s function and biological integrity, Hcy-thiolactone-detoxifying enzymes—PON1, BLMH, BPHL—have evolved. This narrative review provides an account of the biological function of these enzymes and of the consequences of their impairments, leading to the phenotype characteristic of AD. Overall, accumulating evidence discussed in this review supports a hypothesis that Hcy-thiolactone contributes to neurodegeneration associated with a dysregulated Hcy metabolism.
Read the paper
Related studies
- Metabolic Syndrome: Updates on Pathophysiology and Management in 2021
- Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases
- Antioxidants, inflammation and cardiovascular disease
- Application of Metabolomics in Alzheimer’s Disease
- Nutritional Importance of Carotenoids and Their Effect on Liver Health: A Review
- Nutritional essentiality of sulfur in health and disease
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.