PERSONAL DE APOYO
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artículos
Título:
Neuroprotection Targeting Protein Misfolding on Chronic Cerebral Hypoperfusion in the Context of Metabolic Syndrome
Autor/es:
MARÍA I. HERRERA, LUCAS D. UDOVIN, NICOLÁS TORO-URREGO, CARLOS F. KUSNIER , JUAN P. LUACES , MATILDE OTERO-LOSADA AND FRANCISCO CAPANI
Revista:
Frontiers in neuroscience
Editorial:
Frontiers Media
Referencias:
Año: 2018
ISSN:
1662-4548
Resumen:
Metabolic syndrome (MetS) is a cluster of risk factors that lead to microvasculardysfunction and chronic cerebral hypoperfusion (CCH). Long-standing reduction inoxygen and energy supply leads to brain hypoxia and protein misfolding, thereby linkingCCH to Alzheimer?s disease. Protein misfolding results in neurodegeneration as revealedby studying different experimental models of CCH. Regulating proteostasis networkthrough pathways like the unfolded protein response (UPR), the ubiquitin-proteasomesystem (UPS), chaperone-mediated autophagy (CMA), and macroautophagy emergesas a novel target for neuroprotection. Lipoxin A4 methyl ester, baclofen, URB597,N-stearoyl-L-tyrosine, and melatonin may pose potential neuroprotective agents forrebalancing the proteostasis network under CCH. Autophagy is one of the most studiedpathways of proteostatic cell response against the decrease in blood supply to the brainthough the role of the UPR-specific chaperones and the UPS system in CCH deservesfurther research. Pharmacotherapy targeting misfolded proteins at different stages in theproteostatic pathway might be promising in treating cognitive impairment following CCH