Table 1.
The relationship between neurological diseases with genes involved and their methylation.
| Neurologic disorders | Methylation status | Specific genetic loci | Probable effect | symptoms |
|---|---|---|---|---|
| Rett syndrome | Unknown | MECP2 gene | Loss of the activity of the MECP2 gene Reduced BDNF (Na and Monteggia, 2011) | Seizures, cerebral palsy, Repetitive, stereotyped hand movements |
| Alzheimer’s disease | Hypomethylation Hypermethylation |
PS1, BACE1, APP Neprilysin (NEP) |
Upregulation of PS1, BACE1, APP Aβ accumulation (Qazi et al., 2018) |
Progressive dementia |
| Stroke | Hypermethylation | Global methylation (Krupinski et al., 2018) | Sudden onset focal dysfunction | |
| Multiple sclerosis | Hypomethylation | PAD2 | PAD2 Upregulation (Calabrese et al., 2012) |
several neurologic symptoms: muscular weakness, visual symptoms, tremors, intestinal and urinary disorders, cognitive abnormalities |
| Epilepsy | Hypermethylation | reelin | Decreased reelin expression (Henshall and Kobow, 2015) | seizure |
| Parkinson’s disease | Hypomethylation | SNCA intron1 | Increased expression of SNCA (Jowaed et al., 2010) | Rigidity, tremors, shaking, difficulty in walking |
| Immunodeficiency, Centromeric Instability, and Facial Anomalies Syndrome Type1 (ICF1) syndrome | Hypomorphic mutation of DNMT3B | DNMT3B | Reduced the activity of DNMT3B (De Greef et al., 2011) | Mental retardation syndrome |
| ICF2 | Hypomethylation | ZBTB24 | hypomethylation of minor satellite DNA and Centromeric instability (Hardikar et al., 2020) | Mental retardation syndrome |
| ADCA-DN | Hypomethylation | DNMT1 | reduced DNMT1 activity (Kernohan et al., 2016) | Autosomal dominant abnormality with Cerebellar ataxia |
| Amyotrophic lateral sclerosis (ALS) | Hypomethylation | VEGF, SOD1 | No transcriptional silencing (Lu et al., 2013b) | Weakness and atrophy of the muscles |
| schizophrenia | Hypermethylation | GAD67 RELN |
Decreased expression of GAD67and RELN (Grayson and Guidotti, 2013) | Hallucinations, Disorganized thinking |
| Fragile X syndrome | Hypermethylation | FMR1 | FMR1 inactivation (Kumari et al., 2020) | Intellectual disability |
| HSAN1 | Hypomethylation | DNMT1 | Reduced DNMT1 activity (Sun et al., 2014) | Multiple neuropathies |
MECP2: methyl CpG binding protein 2, BDNF: brain-derived neurotrophic factor, PS1: presenilin 1, BACE1: beta-secretase 1, APP: amyloid precursor protein, NEP: neprilysin or neutral endopeptidase, PAD2: peptidyl arginine deiminase, SNCA: Alpha-synuclein, DNMT: DNA methyltransferase, ZBTB24: zinc finger and BTB domain-containing protein 24, VEGF: vascular endothelial growth factor, SOD1: superoxide dismutase type 1, GAD67: glutamate decarboxylase-67, FMR: fragile X mental retardation, Immunodeficiency, Centromeric Instability, and Facial Anomalies Syndrome Type1; ICF1, Immunodeficiency, Centromeric Instability, and Facial Anomalies Syndrome Type 2; ICF2, Amyotrophic lateral sclerosis; ALS. Amyotrophic lateral sclerosis; ALS.