Advances in Genetics and Epigenetic Alterations in Alzheimer’s Disease: A Notion for Therapeutic Treatment
Abstract
:1. Background
2. The Genetics of AD
2.1. Important Susceptibility Genes
2.2. Missing Heritability: Epistasis Explains Undetected Associations in Risk Loci
3. Alzheimer’s and the Epigenome: Filling the Gap?
3.1. Epigenetics Alterations of AD
3.1.1. DNA Methylation
3.1.2. Histone Modifications
3.1.3. Noncoding RNAs
3.1.4. MiRNAs
3.1.5. Piwi-Interacting RNAs
4. Targets for Therapeutic Treatment of AD
4.1. Targeting Key Genes for AD
4.2. Epigenomic Biomarkers for the Treatment of AD
4.3. Aβ Immunotherapy
4.4. HDAC Inhibitors as Therapeutics for AD
5. Concluding Remarks
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Glossary
AD | Alzheimer disease |
LOAD | Late-Onset Alzheimer Disease |
EOAD | Early-Onset Alzheimer Disease |
MCI | Mild cognitive impairment |
CNS | Central nervous system |
CSF | Cerebrospinal fluid |
PFC | prefrontal cortex |
EWAS | Epigenome-wide association study |
GWAS | Genome-wide association study |
NGS | Next-generation sequencing |
WES | Whole-exome sequencing |
WGS | Whole-genome sequencing |
MGAS | Multivariate gene association analysis |
PPI | Protein–protein interaction |
p-Tau | Phosphorylated protein tau |
CGIs | CpG islands |
Aβ | Amyloid-β peptide |
Aβ42 | Amyloid-β 42 |
NFTs | Neurofibrillary tangles |
APP | Amyloid-β precursor protein |
APP-Aβ | β-amyloid domain containing APP |
APP-CTF | APP C-terminal fragment |
BACE1 | β-site amyloid precursor protein cleaving enzyme 1 |
BACE2 | β-site amyloid precursor protein cleaving enzyme 2 |
ApoE | Apolipoprotein E |
ApoE2 | Apolipoprotein ε2 |
ApoE3 | Apolipoprotein ε3 |
ApoE4 | Apolipoprotein ε4 |
APOC1 | Apolipoprotein C1 |
BIN1 | Bridging Integrator 1 |
CLU | Clusterin |
PICALM | Phosphatidylinositol-binding clathrin assembly protein |
TOMM40 | Translocase of outer mitochondrial membrane 40 |
CR1 | Complement receptor type 1 |
ANK1 | Ankyrin 1 |
CDH23 | Cadherin-related 23 |
CaMKIV | Calcium/calmodulin-dependent protein kinase type IV |
DIP2A | Disco-interacting protein 2 homolog A |
RHBDF2 | Inactive rhomboid protein 2 |
RPL13 | 60S ribosomal protein L13 |
SERPINA3 | Serpin family A member 3 |
SERPINF | Serpin family F member |
AICD | APP intracellular domain |
CBP | CREB-binding protein |
MAPT | Microtubule-associated protein Tau |
IGF-I | Insulin-like growth factor 1 |
GLUT4 | Glucose transporter Type 4 |
PSEN1 | Presenilin 1 |
PSEN2 | Presenilin 2 |
SORL1 | Sortilin-related receptor 1 |
ADAM10 | A disintegrin and metalloprotease 10 |
PTM-Hs | Post-translational modification of histones |
DMRs | Differentially methylated regions |
SAM | Methyl donor S-adenosylmethionine |
SIRT1 | Sirtuin 1 |
RNase P | Ribonuclease P |
TER | Telomerase RNA |
TET | Ten–eleven translocation |
SUMO | Small ubiquitin-like modifier |
DGCR8 | Microprocessor complex subunit DGCR8 |
DNMT | DNA methyltransferase |
HAT | Histone acetyltransferase |
HDAC | Histone deacetylase |
HDACi | HDAC inhibitors |
ICBs | Immune checkpoint blockers |
siRC | silencing RNA-induced complex |
RBL2 | Retinoblastoma-like 2 protein |
HDL | High-density lipoproteins |
VLDL | Very low-density lipoprotein |
NF-κB | Nuclear transcription factor kappa B |
ncRNA | Noncoding RNA |
miRNA | MicroRNA |
piRNA | Piwi-interacting RNA |
rRNA | Ribosomal RNA |
snRNA | Small nuclear RNA |
tRNA | Transfer RNA |
snoRNA | Small nucleolar RNA |
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Rabaneda-Bueno, R.; Mena-Montes, B.; Torres-Castro, S.; Torres-Carrillo, N.; Torres-Carrillo, N.M. Advances in Genetics and Epigenetic Alterations in Alzheimer’s Disease: A Notion for Therapeutic Treatment. Genes 2021, 12, 1959. https://doi.org/10.3390/genes12121959
Rabaneda-Bueno R, Mena-Montes B, Torres-Castro S, Torres-Carrillo N, Torres-Carrillo NM. Advances in Genetics and Epigenetic Alterations in Alzheimer’s Disease: A Notion for Therapeutic Treatment. Genes. 2021; 12(12):1959. https://doi.org/10.3390/genes12121959
Chicago/Turabian StyleRabaneda-Bueno, Rubén, Beatriz Mena-Montes, Sara Torres-Castro, Norma Torres-Carrillo, and Nora Magdalena Torres-Carrillo. 2021. "Advances in Genetics and Epigenetic Alterations in Alzheimer’s Disease: A Notion for Therapeutic Treatment" Genes 12, no. 12: 1959. https://doi.org/10.3390/genes12121959