Mitochondria in Neuroprotection by Phytochemicals: Bioactive Polyphenols Modulate Mitochondrial Apoptosis System, Function and Structure

Abstract

In aging and neurodegenerative diseases, loss of distinct type of neurons characterizes disease-specific pathological and clinical features, and mitochondria play a pivotal role in neuronal survival and death. Mitochondria are now considered as the organelle to modulate cellular signal pathways and functions, not only to produce energy and reactive oxygen species. Oxidative stress, deficit of neurotrophic factors, and multiple other factors impair mitochondrial function and induce cell death. Multi-functional plant polyphenols, major groups of phytochemicals, are proposed as one of most promising mitochondria-targeting medicine to preserve the activity and structure of mitochondria and neurons. Polyphenols can scavenge reactive oxygen and nitrogen species and activate redox-responsible transcription factors to regulate expression of genes, coding antioxidants, anti-apoptotic Bcl-2 protein family, and pro-survival neurotrophic factors. In mitochondria, polyphenols can directly regulate the mitochondrial apoptosis system either in preventing or promoting way. Polyphenols also modulate mitochondrial biogenesis, dynamics (fission and fusion), and autophagic degradation to keep the quality and number. This review presents the role of polyphenols in regulation of mitochondrial redox state, death signal system, and homeostasis. The dualistic redox properties of polyphenols are associated with controversial regulation of mitochondrial apoptosis system involved in the neuroprotective and anti-carcinogenic functions. Mitochondria-targeted phytochemical derivatives were synthesized based on the phenolic structure to develop a novel series of neuroprotective and anticancer compounds, which promote the bioavailability and effectiveness. Phytochemicals have shown the multiple beneficial effects in mitochondria, but further investigation is required for the clinical application.

Regular Intake of Pistachio Mitigates the Deleterious Effects of a High Fat-Diet in the Brain of Obese Mice

“…In agreement with our results, several findings indicate that antioxidants of pistachio fruit, including phytosterols and polyphenols, influence mitochondrial dynamics by maintaining the balance between fusion and fission and preventing mitophagy. In addition, modification of autophagy by polyphenols has been proposed as a promising therapeutic strategy [53].…”

Gelidium amansii Attenuates Hypoxia/Reoxygenation-Induced Oxidative Injury in Primary Hippocampal Neurons through Suppressing GluN2B Expression

“…However, if the patients survive, the damage caused by the reperfusion is much higher than that by ischemia itself [17]. The sudden oxygen supply following reperfusion leads to excessive generation of ROS that results in cellular oxidative stress, which follows a cascade of pathological events, such as mitochondrial dysfunction, DNA disintegration, apoptosis and necrosis, and ultimately death of neurons [18,19]. In this study, GAE significantly suppressed ROS accumulation in cultured neurons as opposed to the amount of ROS in untreated neurons and successfully attenuated these pathological consequences.…”

Nutrigenomic Effects of Long-Term Grape Pomace Supplementation in Dairy Cows

“…Some xenobiotics trigger oxidative stress, mitochondrial disfunction and ultimately apoptosis by increasing the expression of Drp1 (mostly) and MFF; among these ones ammonia [63], T2-toxin [64], cadmium [65], and microcystin [66]. However, curcumin, resveratrol, anthocyanins, quercetin and polyphenols inhibit mitochondrial fission through transcriptional and post-translational modifications of Drp-1, MFF as well as of other factors contributing to mitochondrial dynamics, thus preventing cells from oxidative stress [67][68][69]. Therefore, present MFF downregulation might be viewed as a protective effect provoked by GP supplementation against cellular oxidative stress, resulting in minor recruitment and transfer of Drp-1 inside mitochondria and, consequently, no mitochondrial fission/fusion imbalance and apoptosis.…”