Epigenetic Modulation on Tau Phosphorylation in Alzheimer’s Disease

Abstract

Tau hyperphosphorylation is a typical pathological change in Alzheimer’s disease (AD) and is involved in the early onset and progression of AD. Epigenetic modification refers to heritable alterations in gene expression that are not caused by direct changes in the DNA sequence of the gene. Epigenetic modifications, such as noncoding RNA regulation, DNA methylation, and histone modification, can directly or indirectly affect the regulation of tau phosphorylation, thereby participating in AD development and progression. This review summarizes the current research progress on the mechanisms of epigenetic modification associated with tau phosphorylation.

Royal Jelly as an Intelligent Anti-Aging Agent—A Focus on Cognitive Aging and Alzheimer’s Disease: A Review

“…Thus, this pathology results in early nonamnestic features such as dyscalculia and aphasia [ 61 ]. Copper and iron are core redox active transition metals that interact with Aβ to facilitate the electron transfer necessary for the generation of ROS and reactive nitrogen species (RNS) in a reaction that requires tyrosine 10 [ 76 ]. Hydrogen peroxide (H 2 O 2 ), one of the most prominent free radicals produced in AD brains due to oxidative stress, is an uncharged, stable, and freely diffusible ROS.…”

“…As a result, the synthesis, transport, release, and uptake of neurotransmitters gets disrupted. Such interactions promote neurotoxicity, aggravate tau and Aβ deposition, and ultimately lead to more cellular lesions and sporadic neurodegeneration [ 73 , 76 , 80 ]. Finally, progressive damage and death of neurons in several areas of the brain, expressly the hippocampus—an important region for learning and memory—represent the direct cause of clinical manifestations in AD [ 16 , 23 , 28 ].…”

Functional Foods: An Approach to Modulate Molecular Mechanisms of Alzheimer’s Disease

“…Low levels of 5hmC have been detected in several brain regions of late stages AD patients, such as in the neocortex, hippocampus, entorhinal cortex and cerebellum [346][347][348]. On the contrary, 5mC levels were increased in the hippocampus of aging mice, but reduced in APP/PS1 transgenic mice, as well as in the hippocampus, enthorhinal cortex and cerebellum of patients with AD [349].…”

“…In addition, it has been observed that dementia risk increases due to an increase in the SIRT1 level [381]. Regarding this, data associated with epigenetics of AD indicate that low doses of RSV reduce the expression of genes crucial for age-related diseases [348], in particular there is cumulative evidence that RSV activates SIRT1 [348], which leads decreased neuronal loss caused by chronic inflammation.…”

“…CUR, known to reduce the Aβ production by inhibiting glycogen synthase kinase 3-β-mediated PSEN1 activation, inhibits HDAC isoforms 1, 3 and 8, thus participating in reprogramming neural stem cell-directed neurogenesis [348]. It also inhibits HATs [387].…”