Methyl-CpG Binding Protein 2 in Alzheimer Dementia

Abstract

Alzheimer disease is a neurodegenerative disease that constitutes the most common form of dementia without a cure. Alzheimer's Association Reports projected that the social and economic burden and the global prevalence of Alzheimer disease will grow constantly until 2050 [1], demanding immediate attention to research on the treatment and prevention of Alzheimer disease. The pathogenesis of Alzheimer disease is defined by the neurotoxic accumulation of extracellular amyloid-β plaques and intracellular tau neurofibrillary tangles, glial scarring and gliosis, and aberrant alterations in synaptic plasticity, ultimately resulting in severe cognitive impairments and extensive neuronal loss [2]. The cognitive dysfunctions observed in Alzheimer disease primarily consist of memory loss and problems in language or thinking skills. Among the diverse causes of Alzheimer disease identified to date, the foremost studies have revealed that Alzheimer disease

Longitudinal data in peripheral blood confirm that PM20D1 is a quantitative trait locus (QTL) for Alzheimer’s disease and implicate its dynamic role in disease progression

“…In contrast, in samples with hypermethylated PM20D1 (high risk, homozygous alternate allele haplotype carriers, AA/TT), the promoter region is not contacted by the enhancer and transcription does not occur, which results in low PM20D1 expression, and there is no protective effect against Aβ. The role of PM20D1 in AD has since then been further explored [ 22 , 23 ], showing that it is the sole risk gene with consistently enriched promoter hypermethylation in AD patients, and upregulated by Aβ and reactive oxygen species, and being neuroprotective when overexpressed in cell and primary cultures.…”

Differential brain region‐specific expression of MeCP2 and BDNF in Rett Syndrome patients: a distinct grey‐white matter variation

“…This gene encodes for MeCP2 protein, an important epigenetic modulator that controls gene regulation and chromatin organization through binding to methylated DNA [4‐6], and its own expression is also controlled by DNA methylation [7‐11]. Accordingly, MECP2 mutation or altered expression is linked to different neurological disorders including autism spectrum disorders (ASD) [12,13], foetal alcohol spectrum disorders (FASD) [14], MECP2 Duplication Syndrome [15], Alzheimer’s [16] and X‐linked mental disability [13], among others [17]. RTT occurs with an incidence of 1 in 10,000 live female births [18], with extreme rare cases in males [19].…”

Some Molecular and Cellular Stress Mechanisms Associated with Neurodegenerative Diseases and Atherosclerosis

“…SASPs of senescent astrocytes can be a reason of age-related neurodegeneration. In particular, these SASPs can be triggers of Parkinson’, Alzheimer’s diseases and brain disorders [ 194 , 214 , 215 ]. Moreover, SASPs of senescent cells ofsmooth musculature, epithelium and endothelium may be included into mechanisms of the occurrence and development of age-related cardiovascular disease [ 194 , 216 ].…”