Table 1.
The autophagy-related molecular changes in epilepsy animal models and patients.
| Models/Patients | Molecular Changes | Pathological Changes | References |
|---|---|---|---|
| Lafora disease mice | Increased Rab5, p62 protein level, decreased LC3-II levels |
Generalized stimulus-sensitive tonic-clonic seizures | Puri and Suzuki., 2012 [283]; Criado et al., 2012 [284] |
| Pilocarpine-induced model mice | Increased levels of Beclin 1, ATG5, ATG7 and the ratio of LC3II/I | Epilepsy | Ying et al., 2020 [285] |
| N-ethyl-N-nitrosourea (ENU)-induced mice mutants | Vps15 mutation, decreased LC3-II/LC3-I ratio | Cortical atrophy, dysplasia, and epilepsy | Gstrein et al., 2018 [286] |
| TSC1/PTEN KO mice | mTOR hyperactivation, increased Ulk1 phosphorylation |
Epileptogenesis | Yasin et al., 2013 [287] |
| Kainic acid treatment mice | Increased LC3-II levels, elevated ratios of phospho-mTOR/mTOR | Repeated seizures | Shacka et al., 2007 [265] |
| Atg7 KO mice | p62 accumulation | Spontaneous seizures | McMahon et al., 2012 [263] |
| Depdc5 KO mice | Increased mTORC1 signaling | Spontaneous seizures | Yuskaitis et al., 2018 [288] |
| PTEN KO mice + mTOR inhibition | Decreased mTOR activity | Decreased the seizure frequency and death rate | Kwon et al., 2003 [289] |
| Pilocarpine-induced model rats | Increased LC3-II/LC3-I ratio and beclin1 level | Status epilepticus | Cao et al., 2009 [290] |
| Kainic acid treatment rats | mTOR activation | Status epilepticus | Macias et al., 2013 [291] |
| Kainic acid treatment rats + rapamycin | Decreased mTOR activity | Reduced epilepsy | Zeng et al., 2009 [292] |
| Pilocarpine-induced model rats | mTOR activation | Status epilepticus | Buckmaster et al., 2009 [279] |
| Pilocarpine-induced model rats + rapamycin | Decreased mTOR activity | Reduced seizure activity | Huang et al., 2010 [293] |
| Infantile spams/West syndrome rats | mTORC1 pathway overactivation | Spasms, epileptic encephalopathies | Raffo et al., 2011 [294] |
| VPS15 mutation in humans | p62 accumulation | Cortical atrophy, late-onset epilepsy | Gstrein et al., 2018 [286] |
| Beta-propeller protein-associated neurodegeneration patients | De novo mutation in WDR45 | Developmental and epileptic encephalopathies | Carvill et al., 2018 [295] |
| Autosomal dominant lateral temporal epilepsy patients | Reelin mutation | Epilepsy | Dazzo and Nobile., 2022 [260] |
| Vici syndrome patients | EPG5 mutation | Severe seizure disorder, progressive neurodegeneration | Byrne et al., 2016 [296] |
| Pediatric-onset ataxias patients | SNX14 mutation | Progressive cerebellar neurodegeneration, developmental delay, intellectual disability, and seizures | Akizu et al., 2015 [297] |
| Ohtahara syndrome patients | DMXL2 mutation | Intractable seizures and profound developmental disability | Esposito et al., 2019 [298] |
| Children with TBCK p.R126X mutations | Increased LC3-II/LC3-I ratio | Focal and generalized seizures | Ortiz-González et al., 2018 [299] |
| Epilepsy patients | ATG5 gene variant, ATP6V1A/ ATP6AP2 mutation, increased Beclin1 expression | Late-onset epilepsy, temporal lobe epilepsy | Zhang et al., 2021 [300]; Van Damme et al., 2020 [301]; Hirose et al., 2019 [302]; Yang et al., 2022 [303] |
| Focal cortical dysplasia in childhood | mTOR activation, p62 accumulation, TSC1/TSC2 mutation | Epilepsy | Yasin et al., 2013 [287] |
| Human TSC patients | Increased in Ulk1 phosphorylation, p62 accumulation | Cognitive dysfunction, early-onset, intractable epilepsy | McMahon et al., 2012 [263] |
| Hippocampal neuronal culture model of acquired epilepsy | Elevated LC3-II/LC3-I ratio | Acquired epilepsy | Xie et al., 2020 [269] |