The Relationship Between Hyperhomocysteinemia and Neurodegeneration

Abstract

Homocysteine (Hcy) is a key junction in methionine metabolism. In inherited forms of hyperhomocysteinemia patients develop early vascular damage and cognitive decline. Hyperhomocysteinemia is a common consequence of dietary, behavioral and pathological conditions and is epidemiologically related to different diseases, among them neurodegenerative ones are receiving progressively more attention in the last years. Several detrimental mechanisms that see in Hcy a possible promoter seem to be implicated in neurodegeneration (protein structural and functional modifications, oxidative stress, cellular metabolic derangements, epigenetic modifications, pathological aggregates deposition, endothelial damage and atherothrombosis). Interventional studies exploring B group vitamins administration in terms of prevention of Hcy-related cognitive decline and cerebrovascular involvement have shown scant results. In this review, current and possible alternative/complementary approaches are discussed.

Vitamin B12 and Homocysteine Levels Predict Different Outcomes in Early Parkinson's Disease

“…tHcy levels are determined by a number of factors, some of which are modifiable, such as nutritional deficiencies of B12, folate, and B6. Elevated tHcy may have a number of adverse effects, including: functional modifications of proteins; oxidative stress; deposition of pathological aggregates; mitochondrial dysfunction; as well as toxic effects on dopaminergic neurons . This independent association of tHcy with cognitive outcomes is consistent with other large studies in aging .…”

“…Elevated tHcy may have a number of adverse effects, including: functional modifications of proteins; oxidative stress; deposition of pathological aggregates; mitochondrial dysfunction; as well as toxic effects on dopaminergic neurons. 33 This independent association of tHcy with cognitive outcomes is consistent with other large studies in aging. 34,35 Moreover, it is consistent with findings reported in a small, crosssectional study of treated PD patients.…”

Hydrogen Sulfide Inhibits Homocysteine-Induced Neuronal Senescence by Up-Regulation of SIRT1

“…Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it represents an attractive target for therapeutic exploitation [4]. Hcy is an independent risk factor for neurological and cardiovascular disease [30,31]. The level of Hcy in bodies increases with age [32].…”

Hen egg carotenoids (lutein and zeaxanthin) and nutritional impacts on human health: a review

“…These properties of lutein may possibly cause decline in mitochondrial dysfunction and apoptotic death, indicating importance of lutein in treating Alzheimer's. Homocysteine (Hcy), a sulfur containing nonprotein amino acid naturally present in the plasma, is implicated as a risk factor for numerous diseases owing largely to its free radical generating potency (Bonetti, Brombo, & Zuliani, 2016;Bukharaeva, Shakirzyanova, Khuzakhmetova, Sitdikova, & Giniatullin, 2015;Kamat, Vacek, Kalani, & Tyagi, 2015;Paul & Borah, 2015;Sharma, Kumar, Dar, & Singh, 2015). Also, epidemiological studies have found associations between high serum level of Hcy and Alzheimer's disease (AD) progression that eventually leads to vascular dementia (VaD).…”