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.

Keywords: AD, Alzheimer's disease; ALS, amyotrophic lateral sclerosis; AMPK, 5′-adenosine monophosphate-activated protein kinase; ATF6, activating transcription factor 6; ATG, autophagy related genes; Autophagy; BCL-2, B-cell lymphoma 2; BNIP3L, BCL2/adenovirus; COPII, coat protein complex II; Cerebral ischemia; ER, endoplasmic reticulum; FOXO, forkhead box O; FUNDC1, FUN14 domain containing 1; GPCR, G-protein coupled receptor; HD, Huntington's disease; IPC, ischemic preconditioning; IRE1, inositol-requiring enzyme 1; JNK, c-Jun N-terminal kinase; LAMP, lysosomal-associated membrane protein; LC3, light chain 3; LKB1, liver kinase B1; Lysosomal activation; Mitochondria; Mitophagy; Natural compounds; Neurological disorders; Neuroprotection; OGD/R, oxygen and glucose deprivation-reperfusion; PD, Parkinson's disease; PERK, protein kinase R (PKR)-like endoplasmic reticulum kinase; PI3K, phosphatidylinositol 3-kinase; ROS, reactive oxygen species; SQSTM1, sequestosome 1; TFEB, transcription factor EB; TIGAR, TP53-induced glycolysis and apoptosis regulator; ULK, Unc-51- like kinase; Uro-A, urolithin A; eIF2a, eukaryotic translation-initiation factor 2; mTOR, mechanistic target of rapamycin; ΔΨm, mitochondrial membrane potential.

Graphical abstract

Figure 1

Autophagic processes amenable to therapeutic modulation. Several natural compounds are available to activate or inhibit autophagy at the indicated phases of autophagy.