Natural compounds modulate the autophagy with potential implication of stroke

Abstract

Stroke is considered a leading cause of mortality and neurological disability, which puts a huge burden on individuals and the community. To date, effective therapy for stroke has been limited by its complex pathological mechanisms. Autophagy refers to an intracellular degrading process with the involvement of lysosomes. Autophagy plays a critical role in maintaining the homeostasis and survival of cells by eliminating damaged or non-essential cellular constituents. Increasing evidence support that autophagy protects neuronal cells from ischemic injury. However, under certain circumstances, autophagy activation induces cell death and aggravates ischemic brain injury. Diverse naturally derived compounds have been found to modulate autophagy and exert neuroprotection against stroke. In the present work, we have reviewed recent advances in naturally derived compounds that regulate autophagy and discussed their potential application in stroke treatment.

LncRNA FOXD2-AS1 Protects Against Cerebral Ischemia-Reperfusion Injury Through miR-3144-5p/ KCTD15 Axis

“…With regard to the death reason, ischemic stroke ranks third in developing countries and is a leading cause of disability especially in China (Ahsan, Liu et al 2021). The morbidity of stroke has increased with increased life expectancy.…”

Dysregulation of mTOR Signaling after Brain Ischemia

“…Inversely, in nutrient-poor conditions, reduced mTORC1 activity induces autophagy, which leads to the removal of proteins and organelles to compensate for nutrient starvation. As we described previously, a reduction in glucose levels induces AMPK activation, which phosphorylates Raptor, which in turn inhibits mTORC1 and triggers autophagy [ 73 , 79 , 80 ]. Inactivation of mTORC1 under starvation conditions prevents the maintenance of Ser 757 phosphorylation of ULK1, which induces autophagy initiation [ 81 ].…”

“…Furthermore, mTORC1 is a key player in the regulation of autophagy ( Figure 4 ). It induces this catabolic mechanism and facilitates the fusion of the autophagosome with the lysosome, a key step in this process [ 73 ]. In nutrient-rich conditions, active mTORC1 inhibits autophagy by phosphorylating Unc-51-like kinase 1 (ULK1) or UV radiation resistance-associated gene protein (UVRAG), among others [ 74 , 75 , 76 , 77 , 78 ].…”

Molecular Mechanisms and Therapeutic Potential of α- and β-Asarone in the Treatment of Neurological Disorders

“…Autophagy activation can upregulate the clearance of protein aggregates, prevent mitochondrial damage, control axon homeostasis and neurogenesis, ensure cell survival, and reduce growth factor deficiency and ER stress, with potential therapeutic benefits in slowing the pathological progression of AD, PD, and other neurodegenerative diseases [ 136 , 137 ]. Beclin-1, phosphorylated (p)-Akt, and mammalian target of rapamycin (mTOR) are known autophagy regulators, and some plant-derived secondary metabolites have been shown to exert neuroprotective effects via the stimulation of autophagy through both mTOR-dependent and independent mechanisms [ 138 ]. In a 6-OHDA-induced PD mouse model, β-asarone treatment significantly decreased the levels of both mRNA and protein of Beclin-1 and LC3B, and increased p62 expression, indicating autophagy activation [ 29 ].…”