Neuroprotection Targeting Protein Misfolding on Chronic Cerebral Hypoperfusion in the Context of Metabolic Syndrome
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 misfoldi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-05-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2018.00339/full |
| _version_ | 1817992731989901312 |
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| author | María I. Herrera María I. Herrera Lucas D. Udovin Nicolás Toro-Urrego Carlos F. Kusnier Juan P. Luaces Matilde Otero-Losada Francisco Capani Francisco Capani Francisco Capani |
| author_facet | María I. Herrera María I. Herrera Lucas D. Udovin Nicolás Toro-Urrego Carlos F. Kusnier Juan P. Luaces Matilde Otero-Losada Francisco Capani Francisco Capani Francisco Capani |
| author_sort | María I. Herrera |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T01:30:10Z |
| format | Article |
| id | doaj.art-97f20790bb0045039a1d5fb7abf6869c |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-14T01:30:10Z |
| publishDate | 2018-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-97f20790bb0045039a1d5fb7abf6869c2022-12-22T02:20:14ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-05-011210.3389/fnins.2018.00339346686Neuroprotection Targeting Protein Misfolding on Chronic Cerebral Hypoperfusion in the Context of Metabolic SyndromeMaría I. Herrera0María I. Herrera1Lucas D. Udovin2Nicolás Toro-Urrego3Carlos F. Kusnier4Juan P. Luaces5Matilde Otero-Losada6Francisco Capani7Francisco Capani8Francisco Capani9Centro de Investigaciones en Psicología y Psicopedagogía, Facultad de Psicología y Psicopedagogía, Universidad Católica Argentina, Buenos Aires, ArgentinaInstituto de Investigaciones Cardiológicas (ININCA), Universidad de Buenos Aires (UBA-CONICET), Buenos Aires, ArgentinaInstituto de Investigaciones Cardiológicas (ININCA), Universidad de Buenos Aires (UBA-CONICET), Buenos Aires, ArgentinaInstituto de Investigaciones Cardiológicas (ININCA), Universidad de Buenos Aires (UBA-CONICET), Buenos Aires, ArgentinaInstituto de Investigaciones Cardiológicas (ININCA), Universidad de Buenos Aires (UBA-CONICET), Buenos Aires, ArgentinaInstituto de Investigaciones Cardiológicas (ININCA), Universidad de Buenos Aires (UBA-CONICET), Buenos Aires, ArgentinaInstituto de Investigaciones Cardiológicas (ININCA), Universidad de Buenos Aires (UBA-CONICET), Buenos Aires, ArgentinaInstituto de Investigaciones Cardiológicas (ININCA), Universidad de Buenos Aires (UBA-CONICET), Buenos Aires, ArgentinaFacultad de Medicina, Universidad Católica Argentina, Buenos Aires, ArgentinaUniversidad Autónoma de Chile, Santiago de Chile, ChileMetabolic 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.https://www.frontiersin.org/article/10.3389/fnins.2018.00339/fullmetabolic syndromechronic cerebral hypoperfusionneuroprotectionprotein misfoldingendoplasmic reticulum stresschaperones |
| spellingShingle | María I. Herrera María I. Herrera Lucas D. Udovin Nicolás Toro-Urrego Carlos F. Kusnier Juan P. Luaces Matilde Otero-Losada Francisco Capani Francisco Capani Francisco Capani Neuroprotection Targeting Protein Misfolding on Chronic Cerebral Hypoperfusion in the Context of Metabolic Syndrome Frontiers in Neuroscience metabolic syndrome chronic cerebral hypoperfusion neuroprotection protein misfolding endoplasmic reticulum stress chaperones |
| title | Neuroprotection Targeting Protein Misfolding on Chronic Cerebral Hypoperfusion in the Context of Metabolic Syndrome |
| title_full | Neuroprotection Targeting Protein Misfolding on Chronic Cerebral Hypoperfusion in the Context of Metabolic Syndrome |
| title_fullStr | Neuroprotection Targeting Protein Misfolding on Chronic Cerebral Hypoperfusion in the Context of Metabolic Syndrome |
| title_full_unstemmed | Neuroprotection Targeting Protein Misfolding on Chronic Cerebral Hypoperfusion in the Context of Metabolic Syndrome |
| title_short | Neuroprotection Targeting Protein Misfolding on Chronic Cerebral Hypoperfusion in the Context of Metabolic Syndrome |
| title_sort | neuroprotection targeting protein misfolding on chronic cerebral hypoperfusion in the context of metabolic syndrome |
| topic | metabolic syndrome chronic cerebral hypoperfusion neuroprotection protein misfolding endoplasmic reticulum stress chaperones |
| url | https://www.frontiersin.org/article/10.3389/fnins.2018.00339/full |
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