Table 1.
The main proteins associated with epilepsy and their contributions to the phenotype.
| Tissue | Method | Protein | ID | Relation | Biological effect | Reference |
|---|---|---|---|---|---|---|
| Focal epilepsies | ||||||
| Temporal lobe epilepsy | ||||||
| Hipp | SPCT | Mitochondrial complex I (NADH dehydrogenase). | NADH | Decrease | Excitability and selective neuronal vulnerability. | Kunz et al. (2000) |
| Increased calcium ions in the cytosolic environment. | ||||||
| Hipp | IHC + WB | Neuronal nitric oxide synthase. | nNOS | Decrease | Decreased neurotransmitter release and ion channel dynamics. | Leite et al. (2002) |
| Hipp | 2DE + MALDI/TOF | Collapsin response mediator protein 2. | CRMP-2 | Decrease | Aberrant axonal reorganization. | Czech et al. (2004) |
| Hipp | 2DE + MS | Acyl-CoA thioester hydrolase. | ACOT | Decrease | Fatty acid metabolism. | Yang et al. (2004) |
| Hipp | 2DE + MALDI-TOF | Apolipoprotein A-I | ApoAI | Increase | BBB integrity | Yang et al. (2005) and He et al. (2006) |
| Hipp | 2DE + MALDI-TOF | Dimethylarginine dimethylaminohydrolase 1. | DDAH1 | Decrease | Decrease of neurotransmitter release. | He et al. (2006) |
| Hipp | 2DE + MALDI-TOF | Glutamine synthetase | GS | Decrease | Excitotoxicity | He et al. (2006) |
| Hipp | 2DE + MALDI-TOF | 4-aminobutyrate transaminase. | ABAT | Decrease | Glutamate metabolism | He et al. (2006) |
| Hipp | 2DE + MALDI-TOF | Uracil DNA glycosylase | UNG | Decrease | Neuronal death | He et al. (2006) |
| Hipp | 2DE + MALDI-TOF | Silent information regulator 2 protein. | SIR2 | Decrease | DNA repair and cytoprotection. | He et al. (2006) |
| Hipp | 2DE + MALDI-TOF | Alpha-crystallin B | CRYAB | Decrease | Inhibits the aggregation of unfolded proteins. | He et al. (2006) and Keren-Aviram et al. (2018) |
| Hipp | 2DE + MALDI-TOF | Neurofilament 3/Septin-8/alpha tubulin, isoform 1/beta tubulin. | NEF3/Sept8/α-1-tubulin/β-tubulin. | Decrease | Cytoskeleton damage | He et al. (2006) |
| Hipp | 2DE + MALDI-TOF | Dihydropyrimidinase-like 2 | DPYSL2 | Decrease | Cytoskeleton damage | He et al. (2006) and Persike et al. (2012) |
| Hipp | 2DE + MALDI-TOF | Beta tubulin, isoform 5/Ezrin/Vinculin | β5-tubulin/EZR/VCL. | Increase | Cytoskeleton damage | Yang et al. (2006) |
| Hipp | 2DE + MALDI-TOF | Profilin II | PFN2 | Decrease | Cytoskeleton damage | Yang et al. (2006) |
| Hipp | 2DE + MALDI-TOF | Neuronal tropomodulin | TMOD2 | Decrease | Neuronal death and cytoskeleton integrity. | Yang et al. (2006) |
| Hipp | 2DE + MALDI-TOF | Peroxiredoxin 3/ Peroxiredoxin 6 | PRDX3/PRDX6 | Decrease/increase | Attack to reactive oxygen species. | Yang et al. (2006) |
| Hipp | 2DE + MALDI-TOF | T complex protein I alpha | TCP1 | Decrease | Cytoskeleton structure | Yang et al. (2006) |
| Hipp | 2DE + MALDI-TOF | Mitogen-activated protein kinase kinase 1. | MPKK1 | Decrease | Phosphorylation of cytoskeleton proteins. | Yang et al. (2006) |
| Hipp | 2DE + MALDI-TOF | Synaptotagmin I | Syt I | Decrease | Regulation of neurotransmitter release and transport. | Yang et al. (2006) |
| Hipp | 2DE + MALDI-TOF | Alpha-synuclein | SNCA | Decrease/increase | Regulation of neurotransmitter release and transport. | Yang et al. (2006) and Keren-Aviram et al. (2018) |
| Hipp | 2DE + MALDI-TOF | Spectrin alpha chain, isoform 3 | SPTAN1 | Decrease | Electrophysiological activity of the NMDA receptor. | Persike et al. (2012) |
| Hipp | 2DE + MALDI-TOF | Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex, mitochondrial. | DLAT | Increase | Metabolic disturbance and oxidative damage. | Persike et al. (2012) |
| Hipp | 2DE + MALDI-TOF | Parkinson disease protein 7 | PARK7 | Presence | Protection against oxidative stress and cell death in this condition. | Persike et al. (2012) |
| Hipp | 2DE + MALDI-TOF | Glutathione S transferase P | GSTP1 | Presence | Hydrophobic electrophiles maintenance. | Persike et al. (2012) |
| Hipp | 2DE + MALDI-TOF | Heat shock-related 70 kDa protein 2 | HSPA2 | Increase | Cytoskeleton development. | Persike et al. (2012) |
| Hipp | MALDI MSI/MS | Neuropeptide Y | NPY | Increase | Seizure induces neurogenesis. | Mériaux et al. (2014) |
| Hipp | MALDI MSI/MS | Somatostatin 1 | Somatostatin | Increase | Neuromodulator | Mériaux et al. (2014) |
| Hipp | LC-LTQ MS/MS | Leucine-rich glioma inactivated 1. | LIGI1 | Presence | Male autosomal dominant partial epilepsy with auditory features (ADPEAF). | Mériaux et al. (2014) |
| Neocort | LC/MS | Collapsin response mediator protein 2. | CRMP-2 | Increase | Synaptic plasticity related to the epileptic neocortex. | Keren-Aviram et al. (2018) |
| Neocort | LC/MS | Glial fibrillary acidic protein. | GFAP | Decrease | BBB function and cell communication. | Keren-Aviram et al. (2018) |
| Neocort | LC/MS | Guanine nucleotide-binding protein G(o) subunit α/LIM and SH3 protein 1. | GNAO1/LASP1 | Decrease | Astrocyte origin | Keren-Aviram et al. (2018) |
| Neocort | LC/MS | Synapsin II/Stathmin 1 | SYN2/STMN1 | Increase | Neuritogenesis and synaptic transmission. | Keren-Aviram et al. (2018) |
| Hipp | LC/MS | O-GlcNAcase | GOA | Absence | Increase OGlcNacetylation in tissues. | Sánchez et al. (2019) |
| Hipp | IHC | Mitochondrial ATP synthase | ATP5B | Decrease | Neuronal cell maintenance | Mota et al. (2019) |
| Focal cortical dysplasia | ||||||
| Neocort | LC-MS/MS + WB + IHC | Fascin/dihydropyrimidinase-related protein 1/microtubule-associated protein 4. | FSCN1/CRMP1/MAP4 | Increase | Neuron migration, neurite outgrowth, and abnormal dendrite orientation. | Qin et al. (2017) |
| Neocort | LC-MS/MS + WB + IHC | Protein NDRG1 | NDRG1 | Increase | Reactive oligodendroglial hyperplasia. | Qin et al. (2017) |
| Neocort | LC-MS/MS + WB + IHC | Peroxiredoxin-6 | PRDX6 | Decrease | Oxidative stress | Qin et al. (2017) |
| Neocort | LC-MS/MS + WB + IHC | Prosaposin | PSAP | Decrease | Neuroprotection/neurotoxicity. | Qin et al. (2017) |
| Tuberous sclerosis | ||||||
| Tubers | LC-MS/MS | Hamartin | TSC1 | Decrease | Synaptic signaling and inflammation. | Dombkowski et al. (2016) |
| Neocort | LC-MS/MS | Brefeldin A-inhibited guanine nucleotide-exchange protein 2/neuronal migration protein doublecortin. | ARFGEF2/DCX | Decrease/increase | Intellectual disability and abnormal neuronal migration. | Liu et al. (2020) |
| Neocort | LC-MS/MS | Ubiquitin-like protein ATG12. | ATG12 | Decrease | Autophagy | Liu et al. (2020) |
| Neocort | LC-MS/MS | Potassium voltage-gated channel subfamily A member 2. | KCNA2/KCNA2B | Decrease | Membrane excitability. | Liu et al. (2020) |
2DE, two-dimensional electrophoresis; BBB, blood-brain barrier; Hipp, hippocampus; IHC, immunohistochemistry; LC, liquid chromatography; MALDI, matrix-assisted laser desorption ionization; MS, mass spectrometry; Neocort, neocortex; SPCT, spectrophotometry; TOF, time of flight; WB, Western Blot.