Table 1.
Summary of in vivo studies testing PQQ neuroprotection in models of neurodegenerative diseases
| Disease | Species | PQQ dose | Route | Overall outcome | Reference |
|---|---|---|---|---|---|
| AD | Mouse | 6, 12 mg/kg/d (given as Li3PQQ) | Gastric gavage daily for 8 wk | Improved cognitive performance and hippocampal synaptic plasticity; reduced accumulation of amyloid and phosphorylated tau | Zhao et al., 2014 |
| AD | Rat | 2 mg/kg for water administration + 20 mg/kg/d supplementation | Water from weaning to 6 mon + supplementation by oral gavage for 30 d | Prevented cognitive impairment and improved synaptosomes’ bioenergetic capacity | Martino Adami et al., 2017 |
| Epileptic seizures | Rat | 20 mg/kg | i.p. injection 30 min before the induction of seizures | Reduced behavioral seizures | Sanchez et al., 2000 |
| Hypoxia/ischemic brain | Rat | 10, 20 mg/kg | i.p. injection either before or after hypoxia | Reduced infarct size | Jensen et al., 1994 |
| ICH | Rat | 5, 10 mg/kg | i.p. injection every 24 h for 2 wk before IHC and for different time points after injury (1, 2, 3, 5, 7 d) | Improved locomotor function; reduced hematoma volume and brain edema; decreased ROS and apoptosis | Lu et al., 2015 |
| PD | Rat | 6 μL of 333 μM (low dose) or 4 μL 1.5 mM (high dose) | Intracerebral injection together with rotenone (inducer of PD) | Prevented cognitive decline; decreased neural loss; increased antioxidant ability; increased expression of mitochondrial complex I markers, tyrosine hydroxylase, and vesicular monoamine transporter 2 | Qin et al., 2015 |
| PD | Rat | 0.4, 2, 10 mg/kg/d | i.p. injection daily for 8 wk | Prevented cognitive decline; decreased neural loss; increased antioxidant ability; increased expression of mitochondrial complex I Ndufs1/4 and tyrosine hydroxylase | Zhang et al., 2016 |
| PD | Rat | 0.4, 2, 10 mg/kg/d | i.p. injection daily for 8 wk | Increased levels of PGC-1α, TFAM, Drp-1 and Mfn2 | Lu et al., 2018 |
| PD | Mouse | 0.8, 4, 20 mg/kg/d | i.p. injection daily for 1, 2, or 3 wk | Reduced locomotor deficits and nigral dopaminergic neuron loss; diminished reduction of mitochondria number and their morphological disruption; blocked reduction in the expression of PGC-1α and TFAM | Cheng et al., 2021 |
| PD | Fruit fly | 0.3 mM | Supplemented in the cornmeal-agar medium for 25 d | Increased PPL1 dopaminergic neurons and mitochondrial area | Cheng et al., 2021 |
| Retinal ganglion cell-related stress | Mouse | 20 mg/kg/d | i.p. injection daily | Reduced retinal ganglion cell loss | Canovai et al., 2023 |
| Reversible middle cerebral artery occlusion | Rat | 1, 3, 10 mg/kg | Intravenous injection at the initiation or after ischemia | Reduced brain infarct size and improved neurobehavioral scores | Zhang et al., 2006 |
| Schizophrenia | Mouse | 0.2, 2, 20 μg/kg/d | i.p. injection for 60 d | Reduced stereotypical behaviors, ataxia, learning and memory deficits | Zhou et al., 2014 |
| Schizophrenia | Mouse | 5 μg/mL | Drinking water during pregnancy and after birth of the pups | Reduced stereotypical behaviors, ataxia, learning and memory deficits, social interaction disorders, depression | Peng et al., 2022 |
| SCI | Rat | 5 mg/kg | i.p. injection after the injury | Improved locomotor activity and neuronal morphology; reduced inflammation and apoptosis | Zhou et al., 2021 |
| SCI | Rat | 5 mg/kg | i.p. injection immediately after injury and once every 24 h for 7 d | Recovered locomotor function; reduced lesion size; increased axonal density | Hirakawa et al., 2009 |
| TBI | Rat | 2 mM | Microinjected intracerebrally after TBI | Reduced neuronal apoptosis; improved electroencephalographic responses | Zhang et al., 2017 |
| TBI | Rat | 1, 2 mM | Not specified | Reduced brain apoptosis | Ye et al., 2017 |
| TBI | Rat | 5, 7, 10 mg/kg | i.p. injection for 3 d before TBI and consecutively until the end of the experiment (9 d) | Improved behavioral performances and reduced brain injury | Zhang et al., 2012a |
AD: Alzheimer’s disease; Drp-1: dynamin-related protein-1; ICH: intracerebral hemorrhage; Mfn2: mitofusin 2; Ndufs: NADH:ubiquinone oxidoreductase core subunit; PD: Parkinson’s disease; PGC-1α: peroxisome proliferator-activated receptor-gamma coactivator-1α; PPL1: protocerebral posterior lateral 1; ROS: reactive oxygen species; SCI: spinal cord injury; TBI: traumatic brain injury; TFAM: mitochondrial transcription factor A.