Methyl-CpG Binding Protein 2 in Alzheimer Dementia
Despite decades of research on Alzheimer disease, understanding the complexity of the genetic and molecular interactions involved in its pathogenesis remains far from our grasp. Methyl-CpG Binding Protein 2 (MeCP2) is an important epigenetic regulator enriched in the brain, and recent findings have...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Korean Continence Society
2019-11-01
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| Series: | International Neurourology Journal |
| Subjects: | |
| Online Access: | http://www.einj.org/upload/pdf/inj-1938196-098.pdf |
| _version_ | 1818312685884801024 |
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| author | Baeksun Kim Yunjung Choi Hye-Sun Kim Heh-In Im |
| author_facet | Baeksun Kim Yunjung Choi Hye-Sun Kim Heh-In Im |
| author_sort | Baeksun Kim |
| collection | DOAJ |
| description | Despite decades of research on Alzheimer disease, understanding the complexity of the genetic and molecular interactions involved in its pathogenesis remains far from our grasp. Methyl-CpG Binding Protein 2 (MeCP2) is an important epigenetic regulator enriched in the brain, and recent findings have implicated MeCP2 as a crucial player in Alzheimer disease. Here, we provide comprehensive insights into the pathophysiological roles of MeCP2 in Alzheimer disease. In particular, we focus on how the alteration of MeCP2 expression can impact Alzheimer disease through risk genes, amyloid-β and tau pathology, cell death and neurodegeneration, and cellular senescence. We suggest that Alzheimer disease can be adversely affected by upregulated MeCP2-dependent repression of risk genes (MEF2C, ADAM10, and PM20D1), increased tau accumulation, and neurodegeneration through neuronal cell death (excitotoxicity and apoptosis). In addition, we propose that the progression of Alzheimer disease could be caused by reduced MeCP2-mediated enhancement of astrocytic and microglial senescence and consequent glial SASP (senescence-associated secretory phenotype)-dependent neuroinflammation. We surmise that any imbalance in MeCP2 function would accelerate or cause Alzheimer disease pathogenesis, implying that MeCP2 may be a potential drug target for the treatment and prevention of Alzheimer disease. |
| first_indexed | 2024-12-13T08:21:47Z |
| format | Article |
| id | doaj.art-c0e929ddf940437880fdde2382ce0547 |
| institution | Directory Open Access Journal |
| issn | 2093-4777 2093-6931 |
| language | English |
| last_indexed | 2024-12-13T08:21:47Z |
| publishDate | 2019-11-01 |
| publisher | Korean Continence Society |
| record_format | Article |
| series | International Neurourology Journal |
| spelling | doaj.art-c0e929ddf940437880fdde2382ce05472022-12-21T23:53:59ZengKorean Continence SocietyInternational Neurourology Journal2093-47772093-69312019-11-0123Suppl 2S728110.5213/inj.1938196.098817Methyl-CpG Binding Protein 2 in Alzheimer DementiaBaeksun Kim0Yunjung Choi1Hye-Sun Kim2Heh-In Im3 Convergence Research Center for Diagnosis, Treatment and Care System of Dementia (DTC), Korea Institute of Science and Technology (KIST), Seoul, Korea Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea Department of Pharmacology, Seoul National University College of Medicine, Seoul, Korea Convergence Research Center for Diagnosis, Treatment and Care System of Dementia (DTC), Korea Institute of Science and Technology (KIST), Seoul, KoreaDespite decades of research on Alzheimer disease, understanding the complexity of the genetic and molecular interactions involved in its pathogenesis remains far from our grasp. Methyl-CpG Binding Protein 2 (MeCP2) is an important epigenetic regulator enriched in the brain, and recent findings have implicated MeCP2 as a crucial player in Alzheimer disease. Here, we provide comprehensive insights into the pathophysiological roles of MeCP2 in Alzheimer disease. In particular, we focus on how the alteration of MeCP2 expression can impact Alzheimer disease through risk genes, amyloid-β and tau pathology, cell death and neurodegeneration, and cellular senescence. We suggest that Alzheimer disease can be adversely affected by upregulated MeCP2-dependent repression of risk genes (MEF2C, ADAM10, and PM20D1), increased tau accumulation, and neurodegeneration through neuronal cell death (excitotoxicity and apoptosis). In addition, we propose that the progression of Alzheimer disease could be caused by reduced MeCP2-mediated enhancement of astrocytic and microglial senescence and consequent glial SASP (senescence-associated secretory phenotype)-dependent neuroinflammation. We surmise that any imbalance in MeCP2 function would accelerate or cause Alzheimer disease pathogenesis, implying that MeCP2 may be a potential drug target for the treatment and prevention of Alzheimer disease.http://www.einj.org/upload/pdf/inj-1938196-098.pdfmecp2alzheimer diseaserisk genesneurodegenerationsenescenceneuroinflammation |
| spellingShingle | Baeksun Kim Yunjung Choi Hye-Sun Kim Heh-In Im Methyl-CpG Binding Protein 2 in Alzheimer Dementia International Neurourology Journal mecp2 alzheimer disease risk genes neurodegeneration senescence neuroinflammation |
| title | Methyl-CpG Binding Protein 2 in Alzheimer Dementia |
| title_full | Methyl-CpG Binding Protein 2 in Alzheimer Dementia |
| title_fullStr | Methyl-CpG Binding Protein 2 in Alzheimer Dementia |
| title_full_unstemmed | Methyl-CpG Binding Protein 2 in Alzheimer Dementia |
| title_short | Methyl-CpG Binding Protein 2 in Alzheimer Dementia |
| title_sort | methyl cpg binding protein 2 in alzheimer dementia |
| topic | mecp2 alzheimer disease risk genes neurodegeneration senescence neuroinflammation |
| url | http://www.einj.org/upload/pdf/inj-1938196-098.pdf |
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