Strategies for the Modulation of Mitochondrial Metabolism and Activity in the Treatment of Neurodegenerative Diseases: A Systematic Review

Neurodegenerative diseases are currently raising their prevalences and new preclinical low-cost investigations of drug design are urging. This systematic review extensively overviews strategies that use zebrafish assays to investigate modulations of mitochondrial function as new therapies against these diseases. The review was performed following an electronic search of different databases (PubMed, Embase, Scopus and Web of Science) after the PRISMA procedure. Articles published in the English language were identified and screened based on the keywords used: mitochondrial metabolism, therapy, neurodegenerative diseases and zebrafish. Following 176 entries, exclusion criteria reduced the record to 34 final studies. These studies investigate 24 natural, 6 semisynthetic, 5 synthetic and 2 compounds of not-determined origin to ameliorate 9 prevalent diseases: ARSACS, Alzheimer’s, Parkinson’s, Huntington’s diseases, Leigh and Wolfram syndromes, Amyotrophic lateral sclerosis, Limb – girdle muscular dystrophy 2G and hyperglycemia-associated amnesia. Most studies, 22, are focused on potential therapies against Parkinson´s disease that modulate mitochondrial activity in response to endoplasmic reticulum stress/unfolded protein response (4 cases), ubiquitin-dependent mitophagy and receptor-mediated mitophagy (5 cases), or iNOS/NO pathway (1 cases) among others. To conclude, zebrafish have become an effective model for screening potential drugs for neurodegenerative diseases with symptomatology difficult to replicate in rodent models.