Neuroprotection targeting protein misfolding on chronic cerebral hypoperfusion in the context of metabolic syndrome
MetadataShow full item record
Metabolic syndrome (MetS) is a cluster of risk factors that lead to microvascular dysfunction and chronic cerebral hypoperfusion (CCH). Long-standing reduction in oxygen and energy supply leads to brain hypoxia and protein misfolding, thereby linking CCH to Alzheimer's disease. Protein misfolding results in neurodegeneration as revealed by studying different experimental models of CCH. Regulating proteostasis network through pathways like the unfolded protein response (UPR), the ubiquitin-proteasome system (UPS), chaperone-mediated autophagy (CMA), and macroautophagy emerges as a novel target for neuroprotection. Lipoxin A4 methyl ester, baclofen, URB597, N-stearoyl-L-tyrosine, and melatonin may pose potential neuroprotective agents for rebalancing the proteostasis network under CCH. Autophagy is one of the most studied pathways of proteostatic cell response against the decrease in blood supply to the brain though the role of the UPR-specific chaperones and the UPS system in CCH deserves further research. Pharmacotherapy targeting misfolded proteins at different stages in the proteostatic pathway might be promising in treating cognitive impairment following CCH. © 2018 Herrera, Udovin, Toro-Urrego, Kusnier, Luaces, Otero-Losada and Capani.
Showing items related by title, author, creator and subject.
Role of c-jun N-terminal kinases (JNKs) in epilepsy and metabolic cognitive impairment (2020) Busquets O.; Ettcheto M.; Cano A.; Manzine P.R.; Sánchez-Lopez E.; Espinosa-Jiménez T.; Verdaguer E.; Castro-Torres R.D.; Beas-Zarate C.; Sureda F.X.; ... (MDPI AG, 2020)
The Triangle of Death in Alzheimer's Disease Brain: The Aberrant Cross-Talk among Energy Metabolism, Mammalian Target of Rapamycin Signaling, and Protein Homeostasis Revealed by Redox Proteomics (2020) Di Domenico F.; Barone E.; Perluigi M.; Butterfield D.A. (Mary Ann Liebert Inc., 2017)
Astrocytes and endoplasmic reticulum stress: A bridge between obesity and neurodegenerative diseases (2020) Martin-Jiménez C.A.; García-Vega Á.; Cabezas R.; Aliev G.; Echeverria V.; González J.; Barreto G.E. (Elsevier Ltd, 2017)