Abnormal Homocysteine Metabolism: An Insight of Alzheimer’s Disease from DNA Methylation

Abstract

Alzheimer’s disease (AD) is a chronic neurodegenerative disease in the central nervous system that has complex pathogenesis in the elderly. The current review focuses on the epigenetic mechanisms of AD, according to the latest findings. One of the best-characterized chromatin modifications in epigenetic mechanisms is DNA methylation. Highly replicable data shows that AD occurrence is often accompanied by methylation level changes of the AD-related gene. Homocysteine (Hcy) is not only an intermediate product of one-carbon metabolism but also an important independent risk factor of AD; it can affect the cognitive function of the brain by changing the one-carbon metabolism and interfering with the DNA methylation process, resulting in cerebrovascular disease. In general, Hcy may be an environmental factor that affects AD via the DNA methylation pathway with a series of changes in AD-related substance. This review will concentrate on the relation between DNA methylation and Hcy and try to figure out their rule in the pathophysiology of AD.

Protective Effects of Dendrobium nobile Lindl. Alkaloids on Alzheimer's Disease-like Symptoms Induced by High-methionine Diet

“…Methionine can be metabolized into S-adenosine methionine (SAM) under the action of methio-nine adenosyltransferase (MAT). SAM is one of the major methyl donors that can be converted to S-adenosine homocysteine (SAH), a methyl group that will be added to the 5-position carbon atom of cytosine to form 5mC, which is involved in epigenetic modifications under the action of methyltransferase [ 13 ]. SAM/SAH is an important indicator of the methylation potential in vivo .…”

“…Hcy is an intermediate product of Met metabolism, and HMD increases the level of Hcy ​​in the serum [ 13 ]. The levels of Hcy and Aβ 1-42 serve as the serum biomarkers of AD [ 55 , 56 ], which not only increase the risk of AD but also further aggravate the symptoms of AD.…”

“…Hcy is an important intermediate product that Met can produce during the metabolism of the body. Hcy is not only a risk factor for diseases, such as vascular dementia (VD) and AD [ 11 , 12 ], but also a biomarker of AD in serum and plasma [ 13 ]. Moreover, elevating Hcy ​​levels caused by homocysteinemia (HHcy) is related to AD-like symptoms induced by an HMD [ 14 , 15 ].…”

Perspective Chapter: Exercise-Eating Pattern and Social Inclusion (EES) is an Effective Modulator of Pathophysiological Hallmarks of Alzheimer’s Disease

“…Another study found that abnormal plasma homocysteine and distressed homocysteine amino acid metabolism are risk factors for intellectual concept [5]. Several potential mechanisms have been studied on the harmful effects of homocysteine amino acid in the brain including oxidative deterioration [16], cerebrovascular impairment [17], DNA destruction [18], and activation of N-methyl-D-aspartate receptors [19]. In the Figure 1, we summarized the various modifiable risk determinants that are responsible for AD pathology.…”

Blood levels of circulating methionine components in Alzheimer’s disease and mild cognitive impairment: A systematic review and meta-analysis

“…This may be related to Hcy being an intermediate product of the one-carbon metabolism and affecting cognitive function by interfering with the DNA/RNA methylation process, resulting in neurodegenerative disease. In general, Hcy seems to be a risk factor that affects AD via the DNA/RNA methylation pathway, through a series of changes in AD-related substances (Pi et al, 2020).…”