Autophagy in vascular dementia and natural products with autophagy regulating activity. (August 2021)

• Record Type: Journal Article
• Authors: Wang, Wenzhe; Qiao, Ou; Ji, Haixia; Zhang, Xinyu; Han, Xiaoying; Zhang, Yi; Wang, Juan; Li, Xia; Gao, Wenyuan
• Is Part Of: Pharmacological research. Volume 170(2021)
• Publication Date: 2021-08
• Subjects: Aβ Amyloid-β peptide -- AIF Apoptosis-Inducing Factor -- AMPK AMP-activated protein kinase -- APOE Apolipoprotein E -- Atg Autophagy related protein -- Baf A1 bafilomycin A1 -- Bax BCL2-Associated X -- BBB Blood brain barrier -- Bcl2 B-cell lymphoma-2 -- Bcl-xl B-cell lymphoma-extra large -- CaMKII Calcium/calmodulin-dependent protein kinase II -- CCH Chronic Cerebral Hypoperfusion -- CNS Central nervous system -- CREB Cyclic AMP response-element binding protein -- DIABLO direct inhibitor of apoptosis protein (IAP)-binding protein with low pI -- ER Endoplasmic reticulum -- FDA Food and Drug Administration -- HIF-1α Hypoxia-inducible factor-1α -- HO-1 Heme oxygenase-1 -- HSYA Hydroxysafflor yellow A -- HtrA2/Omi High-temperature-requirement A2 -- IL-8 Interleukin-8 -- I/R ischemia/reperfusion -- JAK1 Janus kinase-1 -- JNK c-Jun N-terminal kinase -- LAMP lysosomal membrane proteins -- LC3 Microtubule-associated protein 1A/1B-light chain 3 -- LMP Lysosomal permeability -- MAPKs p38 mitogen-activated protein kinases -- MCAO Middle cerebral artery occlusion -- Mcl-1 Myeloid cell leukemia-1 -- MMP Matrix metalloprotein -- mTORC1 mammalian target of rapamycin complex 1 -- NF-κB Nuclear factor kappa B -- NMDA N-methyl-D-aspartate -- Nqo1 NAD(P)H:Quinone Oxidoreductase 1 -- Nrf2 Nuclear erythroid 2-related factor 2 -- OGD oxygen-glucose deprivation model -- PE phosphatidyletanolamine -- PGI2 Prostaglandin I2 -- PI3K phosphatidylinositol 3′-kinase -- PIP2 phosphatidylinositol-4, 5-bisphosphate -- PIP3 phosphatidylinositol-3, 4, 5-triphosphate -- ROS Reactive oxygen species -- SA Schisandrin A -- SIRT1 Sirtuin 1 -- Smac Second mitochondria-derived activator of caspases -- SOD superoxide dismutase -- STAT-1 Signal transducer and activator of transcription-1 -- TNF-α Tumor necrosis factor alpha -- TSC tuberous sclerosis -- TXA2 Thromboxane A2 -- ULK1 UNC-51-like kinase -- VD Vascular dementia -- VEGF vascular endothelial-derived growth factor -- VMP1 Vacuole membrane protein 1 -- Vsp34 Vacuolar Protein Sorting 34 -- WM White matter -- XIAP X-chromosome-linked inhibitor of apoptosis -- 3-MA 3⁃methyl adenine; Vascular dementia -- Chronic cerebral hypoperfusion -- Autophagy -- Natural products; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2021.105756
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: Chronic Cerebral Hypoperfusion(CCH)-induced vascular dementia(VD) is a common neurodegenerative disease which seriously affects the patient's quality of life. Therefore, it is critical to find an effective treatment of VD. Autophagy is a natural regulated mechanism that can remove dysfunctional proteins and organelles, however, over-activation or under-activation can of autophagy can induce the apoptosis of cells. Although autophagy plays a role in the central nervous system is unquestionable, the effects of autophagy in the ischemic brain are still controversial. Some autophagy regulators have been tested, suggesting that both activation and inhibition of autophagy can improve the cognitive function. This article reviews the role of autophagy in CCH-induced VD to discuss whether autophagy has the potential to become a target for drug development and provides several potential compounds for treating vascular dementia. Graphical Abstract: ga1 Highlights: Autophagy is activated in chronic hypoperfusion-induced vascular dementia. Mild to moderate autophagy activation is beneficial for the recovery of vascular dementia. Excessive activation of autophagy can cause apoptosis. Targeted autophagy therapy may be a new direction for the treatment of vascular dementia.