J Nutr Biochem. 2026 Mar:149:110178.
Highlights:
• PQQ is an enzyme cofactor with emerging neuroprotective roles in the CNS.
• Mitochondrial biogenesis is promoted by PQQ through PGC-1α/NRF-1 signaling.
• PQQ reduces oxidative stress and inflammation via Nrf2 activation and NF-κB inhibition.
• PQQ alleviates cognitive decline and neurological injury in preclinical studies.
• PQQ improves folate transport and reduces inflammation in cerebral folate deficiency.
Abstract:
Pyrroloquinoline quinone (PQQ) is an enzyme belonging to the family of quinone cofactors (or quinoproteins) naturally found in soil and food. PQQ was initially discovered as an essential cofactor for bacterial dehydrogenases and has since been reported to be involved in several biological processes important for mammalian growth and development. Animal studies have demonstrated that insufficient dietary intake of PQQ can lead to notable deficits, including impaired growth and compromised reproductive outcomes. In more recent years, PQQ has been recognized for its neuroprotective effects in several in vitro and in vivo models of brain injury and disease, rendering it an attractive compound to be incorporated into treatment strategies for various neurological disorders. More specifically, PQQ has been reported to enhance mitochondrial function and mitigate inflammatory and oxidative stress responses in the central nervous system (CNS) through the activation of several signaling pathways. Additionally, PQQ has emerged as a promising compound that could be incorporated in treatment strategies for cerebral folate deficiency, a pediatric neurological condition characterized by suboptimal folate levels in the cerebrospinal fluid, leading to developmental delays, epilepsy, and other neurological symptoms. This review will address the biochemical properties, mechanism of action, and physiological roles of PQQ with a specific focus on its antioxidant and anti-inflammatory effects as well as its role in enhancing mitochondrial function. The therapeutic implications of these findings will be discussed, emphasizing PQQ's potential as a novel pharmacological approach for the management of neurological disorders, including its emerging role in cerebral folate deficiency.
