List molecules that regulate several mitochondrial functions impaired in neurodegenerative disorder examined under preclinical as well as in clinical trials
| Drugs/molecule | Disease | Type of studies | Outcomes | References |
|---|---|---|---|---|
| α-lipoic acid | AD | Preclinical and clinical | Neuroprotective effect, learning and memory improvement | [126] |
| Inosine | ALS | Preclinical and clinical | Safety, tolerability, and effective in increasing urate serum levels | [127] |
| Inosine/urate | PD | Preclinical and clinical | Safety, tolerability, and effective in increasing urate serum levels | [128, 129] |
| Melatonin | ALS, PD, AD | Preclinical and clinical | Safety, better sleep, and a decrease in oxidative stress indicators; no advantages for motor activity; no ameliorations in cognitive functions | [130, 131] |
| Mito-Apocynin | AD, PD | Preclinical | Motor deficit & neuroinflammation attenuation (neuroprotection) | [132–134] |
| Mito Q | ALS, AD, HD, PD | Preclinical | Lengthening lifespan, mitigating cognitive decline, and increasing hindlimb strength; preventing the loss of dopaminergic neurons in a 6-OHDA PD mice model and decreasing ROS-induced autophagy while fostering mitochondrial fusion | [135, 136] |
| N-acetylcysteine | AD, PD, HD | Preclinical | An improvement in cognitive and motor impairments; an increase in brain connections, GSH levels, TH and complex 1 activity; protection against neuroinflammation | [137] |
| SKQ1 | AD | Preclinical | Improvements in cognition and behavior (reduction of ROS generation) | [138] |
| Szeto-Schiller tetrapeptides | AD, PD, ALS | Preclinical | Improved anterograde axonal transport and synaptic activity, increased survival and improved behavior in SOD1G93A mice, as well as increased lifespan and improved motor ability | [138, 139] |
| Vitamin C | AD | Preclinical | Protection of mitochondrial morphology (reduction of oxidative stress damage) and prevention of apoptosis | [140] |
| Carotenoids (astaxanthin) | AD | Preclinical | Hippocampal neurons treated with A 1–42 oligomers and astaxanthin are protected from the formation of ROS; decreasing neuroinflammation and synaptotoxic events | [141] |
| Vitamin E | AD | Preclinical, clinical | Vitamin E on glutamate-treated astrocytes: healing of mitochondrial damage (MMP stabilization and decreased lipid peroxidation); additional research on AD sufferers is required | [142–144] |
| Vitamin E | ALS | Preclinical, clinical | Several clinical investigations have revealed contradictory results in terms of delaying the onset and course of ALS, but more research is required | [145] |
| PGC-1α | PD | Preclinical | Synuclein oligomerization in a cell culture model with PGC-1 restoration; animals with the A30P synuclein gene: decreased synuclein oligomerization | [146] |
| Olesoxime | PD, HD | Preclinical | Enhancing mitochondrial function and preventing apoptosis; stabilizing the mitochondrial membrane improvement in behavior and cognition | [147] |
| Olesoxime | SMA | Preclinical, clinical | Efficacy in motor improvement and safety have been confirmed; it could be administered in combinatorial therapy | [148] |
| Curcumin | ALS | Preclinical, clinical | Increased lifespan and slowed illness progression, although more research on various delivery techniques is required | [149] |
| Flavonoids | ALS | Preclinical | Motor performances improvement [prevention of MN (motor neurons) loss] | [145] |
| Quercetin | AD | Preclinical | Improvements in cognitive capabilities, antioxidant activity, MMP and mitochondrial morphological restoration, a reduction in ROS, a rise in ATP levels, and suppression of apoptosis | [149] |
| Resveratrol | AD | Preclinical, clinical | Cognitive decline mitigation | [149] |
| Pramipexol | PD | Preclinical | Neuroprotection (mPTP opening prevention and a decrease in ROS production) | [150] |
ALS: amyotrophic lateral sclerosis; 6-OHDA: 6-hydroxydopamine; MMP: matrix metalloproteinases; MN: motor neurons; SKQ1: Visomitin; SMA: spinal muscular atrophy; TH: thyroid hormone