Table 2.
Drug targeting mitochondrial dysfunction
| Therapeutic | Mechanism | Indication | Ref |
|---|---|---|---|
| General antioxidants | |||
| Vitamin E | General antioxidant | Alzheimer’s Disease (potentially harmful, delay of progression) Mild Cognitive Impairment (no effect) |
(151, 222, 223) |
| Vitamin C | General antioxidant | Alzheimer’s Disease Clinical Trial (potentially harmful) | (151) |
| α-lipoic acid | General antioxidant | Alzheimer’s Disease Clinical Trial (potentially harmful) | (151) |
| Coenzyme Q | General antioxidant | Alzheimer’s Disease Clinical Trial (no effect) Parkinson’s Disease Clinical Trial (no effect) ALS Clinical Trial (no effect) |
(151, 152, 224–226) |
| Curcumin | General antioxidant | Alzheimer’s Disease Clinical Trial (increased plasma Aβ) | (227) |
| Melatonin | General antioxidant | Alzheimer’s Disease Clinical Trial (no effect) | (228) |
| Pramipexole | General antioxidant | Parkinson’s Disease Clinical Trial (no effect) | (229) |
| N-Acetylcysteine | General antioxidant | Parkinson’s Disease Clinical Trial (increase brain and blood glutathione) | (230) |
| Edaravone | General antioxidant | ALS Clinical Trial (no effect) | (153) |
| Mitochondria-targeted therapies | |||
| TPP+-conjugated ROS Scavengers (MitoQ) |
Mitochondria-targeted antioxidant | Parkinson’s Disease Clinical Trial (no effect) | (164) |
| Dimebon (latrepiridine) | L-type calcium channel blocker, MPTP inhibitor | Huntington’s Disease Clinical Trial (no effect) Alzheimer’s Disease Clinical Trial (beneficial phase II, no effect phase III) |
(156–158) |
| Dexpramipexole | Mitochondria-targeted antioxidant | ALS Clinical Trial (no effect) | (231) |
| Aromatic-cationic peptides (SS31 or Bendavia, SS20) | Mitochondria-targeted antioxidant | ALS SOD1 mouse model (delayed onset) MPTP neurotoxicity in mice (neuroprotection) |
(161, 162) |
| Mdivi-1 | General inhibitor of Drp1 | Cell culture model of propofol toxicity (decreased cell death) Cell culture model of Parkinson’s Disease (rescued mitochondrial structural and functional defects) |
(197, 198) |
| P110 | Inhibition of mitochondrial Drp1 recruitment through Fis1 | Cell culture model of Parkinson’s Disease (increased mitochondrial function) Cell culture model and mouse model of Huntington’s Disease (increased mitochondrial function, mouse survival, and mouse behavior). |
(204) (205) |
| CyclosporinA | Calcineurin inhibitor, cyclophilin D inhibitor | No indication (off-target effects leading to immunosuppression). | (218) |
| Antmanide | cyclophilin D inhibitor | (220) | |