Table 1.
Partial list of CNS diseases characterized by mitochondrial dysfunction and evidence of pharmacological induction of MB as therapeutic interventions for each.
| Disease | Mitochondrial Dysfunction | Tested MB Treatments | References |
|---|---|---|---|
| Acute Diseases | |||
| Traumatic Brain Injury | Ischemia: ↓OXPHOS proteins, ↓ATP synthesis, ↓ATP-dependent cellular processes, ↓ion homeostasis Reperfusion: ↑ROS, ↑oxidative stress, ↑Ca2+, mPTP opening, ↑cell death |
Quercetin: ↑PGC-1α, ↓cell death DEX: ↑PGC-1α, ↓cell death, ↑behavior 7,8-DHF: ↑PGC-1α, ↑function SS-31: ↑PGC-1α, ↑function, ↑behavior |
(Li et al., 2018c) (Li et al., 2018a) (Krishna et al., 2017) (Zhu et al., 2018) |
| Spinal Cord Injury |
Formoterol: ↑PGC-1α, ↓cell death, ↑function LY344864: ↑PGC-1α, ↓cell death, ↑function Mitochondrial transplant: ↑pAKT, ↑function, ↓cell death |
(Scholpa et al., 2019a; Scholpa et al., 2019b) (Simmons et al., 2019) (Li et al., 2019) |
|
| Stroke |
Mitochondrial transplant: ↑pAKT, ↓cell death, ↑function Daidzein: ↓cell death, antioxidant Metformin: ↓cell death, ↑behavior Melatonin: ↑mitophagy, antioxidant |
(Chang et al., 2019) (Hayakawa et al., 2016) (Cao et al., 2017) (Andrzejewski et al., 2014; Owen et al., 2000) (Qi et al., 2017) |
|
| Neurodegenerative | |||
| Alzheimer’s Disease | ↓MB, ↑mitochondrial size and structural damage, ↓content, ↑fragmentation, ↑mtDNA mutations |
TZDs: ↑behavior Resveratrol: ↑PGC-1α, ↑behavior, ↑pAKT AICAR: ↑behavior, ↑pAKT Melatonin: ↑PGC-1α, ↑function, ↓Aβ |
(Cheng et al., 2016; Heneka et al., 2015; Risner et al., 2006; Watson et al., 2005) (Vingtdeux et al., 2010) (Wang et al., 2019) |
| Parkinson’s Disease | ↑mtDNA mutations (complex I), ↑oxidative damage, ↓PGC-1α, ↓OXPHOS, ↓homeostasis |
Bezafibrate: ↑PGC-1α, ↑behavior Resveratrol: ↑PGC-1α, ↑function, ↓cell death LY344864: ↑PGC-1α, ↑function, ↓cell death Triterpenoids: ↑Nrf2, antioxidant |
(Tufekci et al., 2011) (Corona and Duchen, 2016) (Peng et al., 2016) (Scholpa et al., 2018a) |
Adaption from (Gibbs et al., 2018c). Arrows indicated increase (↑) and decrease (↓). AICAR: 5-aminoimidazole-4-carboxamide ribonucleotide, ATP: adenosine triphosphate, Ca2+: calcium ion, DEX: dexmedetomidine, ETC: electron transport chain, MB: mitochondrial biogenesis, mPTP: membrane permeability transition pore, mtDNA: mitochondrial DNA, PGC-1α: peroxisome proliferator-activated receptor-γ coactivator 1-α, OXPHOS: oxidative phosphorylation, ROS: reactive oxygen species, TFAM: mitochondrial transcription factor A, TZDs: thiazolidinediones, 7,8-DHF: dihydroxyflavone.