PQQ is also known as pyrroloquinoline quinone or methoxatin. It is a type of quinone, like CoQ10, and has been classified as a B vitamin (Zhang et al., 2012). The molecule was initially isolated from bacteria in 1979, where it acts as a cofactor for dehydrogenases (He et al., 2003). 

As a treatment, PQQ is a strong antioxidant and redox regulator, protecting mitochondria from oxidative stress and ROS (Guan et al., 2015). In fact, it has a scavenging ability 7.4-fold higher than Vitamin C, known as the most active water-soluble antioxidant (Jonscher et al., 2017). However, it can also act as a pro-oxidant depending on the biological environment, varying between the type of cell and concentration (He et al., 2003). At levels of up to 10 μM it behaves mainly as an antioxidant, and levels beyond 50 μM a pro-oxidant (Guan et al., 2015). This duality provides PQQ with strong healing capacities, but several destructive consequences as well. As a pro-oxidant, cell apoptosis can be induced by PQQ via several mitochondrial pathways; these include decreasing ATP levels and disturbing membrane potential. A 2020 study showed great variation in PQQ toxicity thresholds and viability, which was based on cell and model (human or mice) type (Peng et al., 2020). These findings suggest that more cell-specific research needs to be done in order to establish the appropriate levels for PQQ therapies. 

Despite these detriments at higher concentrations, the vast majority of PQQ research has proven its safe and promising benefits. When scientists began researching PQQ presence in animals, high amounts were found in fluids such as breast milk, colostrum, plasma, bile, and synovial fluid (Bishop et al., 1998). The levels in breast milk and colostrum suggest that PQQ has a role in early development; studies done on rats showed that new mothers’ milk contains high levels of PQQ. Concentrations of this compound in chicken eggs were similarly high, further promoting its role in development (Bishop et al., 1998). Furthermore, studies with young mice showed that PQQ-deficient diets led to stunted growth patterns (He et al., 2003).

As an antioxidant, PQQ acts similarly to CoQ10 in that it has been found to react with N-methyl D-aspartate receptors (NMDARs). These reside in cortical neurons receiving glutamate and are extremely important in memory and synaptic plasticity. Such receptors are also susceptible to neurotoxicity; redox modulatory sites on NMDARs get oxidized by free radicals, encouraging the over-activation of the receptor and eventually glutamate toxicity (Aizenman et al., 1992). This type of toxicity is associated with a number of neurodegenerative disorders, including Alzheimer’s, ALS, and Huntington’s (Lewerenz & Maher, 2015). Neuralstem and progenitor cells, which are important in injury and stressful stimuli response in the brain, are also sensitive to glutamate toxicity (Guan et al., 2015). PQQ can oxidize these modulatory sites, providing neuroprotection against a variety of ailments (Aizenman et al., 1992). Since NMDARs are found largely in the hippocampus and cortex, PQQ has the largest effect in this region (Peng et al., 2020). 

PQQ has other pathways of neuroprotection against neurodegenerative diseases. For example, it prevents the accumulation of a specific damaged protein called alpha-synuclein (Zhang et al., 2012), which is associated with Parkinson’s and dementia with Lewy bodies, which are detrimental protein accumulations (Games et al., 2014). PQQ may also act as a treatment for Alzheimer’s by inhibiting the aggregation of beta-amyloid peptides. One study with rat models showed promise in utilizing PQQ as a therapy for traumatic brain injury recovery (Zhang et al., 2012). These are just a few examples of CNS ailments that can have the potential to be treated by this molecule.   

PQQ has a special relationship with mitochondria and consequently metabolism. Research has correlated PQQ deficiencies with fewer mitochondria, and one study utilizing rat models found that PQQ supplementation encouraged mitochondrial biogenesis. PQQ is able to do this by activating peroxisome proliferator-activated receptor-γ coactivator 1-alpha (PGC- 1α) and cAMP response element-binding protein (CREB), both of which are involved with the mitochondrial-creating pathway. The PGC- 1α pathway also plays a part in improving mitochondrial respiration, which assists in antioxidant activity and increasing metabolism (Chowanadisai et al., 2010). Furthermore, PQQ interacts with several other pathways that interact with growth factor receptors (Harris et al., 2013). 

PQQ is an essential nutrient in mammals because it is not synthesized by the mammalian body. Food sources include kiwi fruit, green peppers, parsley, and fermented soybeans. However, it is believed that the main source of this molecule in mammals comes from bacteria, specifically dirt-dwelling ones. Oral supplements are also another way to ingest PQQ, which have been promising since studies have found no instances of toxicity using this method (Akagawa et al., 2016).