Pyrroloquinoline quinone:a potential neuroprotective compound for neurodegenerative diseases targeting metabolism

Pyrroloquinoline quinone is a quinone described as a cofactor for many bacterial dehydrogenases and is reported to exert an effect on metabolism in mammalian cells/tissues.Pyrroloquinoline quinone is present in the diet being available in foodstuffs,conferring the potential of this compound to be supplemented by dietary administration.Pyrroloquinoline quinone’s nutritional role in mammalian health is supported by the extensive deficits in reproduction,growth,and immunity resulting from the dietary absence of pyrroloquinoline quinone,and as such,pyrroloquinoline quinone has been considered as a“new vitamin.”Although the classification of pyrroloquinoline quinone as a vitamin needs to be properly established,the wide range of benefits for health provided has been reported in many studies.In this respect,pyrroloquinoline quinone seems to be particularly involved in regulating cell signaling pathways that promote metabolic and mitochondrial processes in many experimental contexts,thus dictating the rationale to consider pyrroloquinoline quinone as a vital compound for mammalian life.Through the regulation of different metabolic mechanisms,pyrroloquinoline quinone may improve clinical deficits where dysfunctional metabolism and mitochondrial activity contribute to induce cell damage and death.Pyrroloquinoline quinone has been demonstrated to have neuroprotective properties in different experimental models of neurodegeneration,although the link between pyrroloquinoline quinone-promoted metabolism and improved neuronal viability in some of such contexts is still to be fully elucidated.Here,we review the general properties of pyrroloquinoline quinone and its capacity to modulate metabolic and mitochondrial mechanisms in physiological contexts.In addition,we analyze the neuroprotective properties of pyrroloquinoline quinone in different neurodegenerative conditions and consider future perspectives for pyrroloquinoline quinone’s potential in health and disease.

Experimental model of photo-oxidative damage

Background:Retinal degeneration is a common feature of several retinal diseases,such as retinitis pigmentosa and age-related macular degeneration(AMD).In this respect,experimental models of photo-oxidative damage reproduce faithfully photoreceptor loss and many pathophysiological events involved in the activation of retinal cell degeneration.Therefore,such models represent a useful tool to study the mechanisms related to cell death.Their advantage consists in the possibility of modulating the severity of damage according to the needs of the experimenter.Indeed,bright light exposure could be regulated in both time and intensity to trigger a burst of apoptosis in photoreceptors,allowing the study of degenerative mechanisms in a controlled fashion,compared to the progressive and slower rate of death in other genetic models of photoreceptor degeneration.Methods:Here,an exemplificative protocol of bright light exposure in albino rat is described,as well as the main outcomes in retinal function,photoreceptor death,oxidative stress,and inflammation,which characterize this model and reproduce the main features of retinal degeneration diseases.Discussion:Models of photo-oxidative damage represent a useful tool to study the mechanisms responsible for photoreceptor degeneration.In this respect,it is important to adapt the exposure paradigm to the experimental needs,and the wide range of variables and limitations influencing the final outcomes should be considered to achieve proper results.Trial Registration:None.

Experimental models of retinopathy of prematurity

Background:Retinopathy of prematurity(ROP)is considered as the most common reason for blindness in children,particularly in preterm infants.The disease is characterized by the dysregulation of angiogenic mechanisms due to preterm birth,leading ultimately to vascular abnormalities and pathological neovascularization(NV).Retinal detachment and vision loss could represent a concrete risk connected to the most severe forms of ROP,also characterized by inflammation and retinal cell death.Methods:During the last decades,many animal models of oxygen-induced retinopathy(OIR)have been recognized as useful tools to study the mechanisms of disease,since they reproduce the hallmarks typical of human ROP.Indeed,modulation of retinal vascular development by exposure to different oxygen protocols is possible in these animals,reproducing the main pathological phenotypes of the disease.The easy quantification of abnormal NV and the possibility to perform electrophysiologic,histological and molecular analyses on these models,make OIR animals a fundamental instrument in studying the pathophysiology of ROP and the effects of novel treatments against the disease.Discussion:Here,the most commonly used OIR protocols in rodents,such as mice and rats,are described as well as the main pathological outcomes typical of these models.Despite their limitations and variables which should be considered whilst using these models,OIR models display several characteristics which have also been confirmed in human patients,validating the usefulness of such animals in the pre-clinical research of ROP.