Alzheimer’s disease(AD)is the main neurodegenerative disease leading to dementia and cognitive impairment in the elderly.Considering AD to be an epidemic,an increase from the current 50 million to more than 150 milli...Alzheimer’s disease(AD)is the main neurodegenerative disease leading to dementia and cognitive impairment in the elderly.Considering AD to be an epidemic,an increase from the current 50 million to more than 150 million patients is expected by the year 2050.展开更多
Intracerebral hemorrhage (ICH) is the most severe cerebrovascular disease, which represents a leading cause of death and disability in developed countries. However, therapeutic options are limited, so is mandatory t...Intracerebral hemorrhage (ICH) is the most severe cerebrovascular disease, which represents a leading cause of death and disability in developed countries. However, therapeutic options are limited, so is mandatory to investigate repairing processes after stroke in order to develop new therapeutic strategies able to promote brain repair processes. Therapeutic angiogenesis and vasculogenesis hold promise to improve outcome of ICH patients. In this regard, circulating endothelial progenitor cells (EPCs) have recently been suggested to be a marker of vascular risk and endothelial function. Moreover, EPC levels have been associated with good neurological and functional outcome as well as reduced residual hematoma volume in ICH patients. Finally, experimental and clinical studies indicate that EPC might mediate endothelial cell regeneration and neovascularization. Therefore, EPC-based therapy could be an excellent therapeutic option in ICH. In this mini-review, we discuss the present status of knowledge about the possible therapeutic role of EPCs in ICH, molecular mechanisms, and the future perspectives and strategies for their use in clinical practice.展开更多
Epidemiology and physiopathology of ischemic stroke:Every year, around 15 million of people suffer a stroke event all around the world. Among those, around 6.7 million will die, and most of the survivors will suffer s...Epidemiology and physiopathology of ischemic stroke:Every year, around 15 million of people suffer a stroke event all around the world. Among those, around 6.7 million will die, and most of the survivors will suffer some grade of disability.展开更多
Correction:Translational Neurodegeneration(2022)11:58 https://doi.org/10.1186/s40035-022-00329-7 Following publication of this article[1],the authors iden-tified an error in the family name of Alon Monsonego.The incor...Correction:Translational Neurodegeneration(2022)11:58 https://doi.org/10.1186/s40035-022-00329-7 Following publication of this article[1],the authors iden-tified an error in the family name of Alon Monsonego.The incorrect author name is:Alon Monsengo.The correct author name is:Alon Monsonego.The author group has been updated above and the orig-inal article[1]has been corrected.展开更多
Objective To study the association between early growth of haematoma with biomarkers of endothelial dysfunction such as leukoaraiosis(LA)and the soluble tumour necrosis factor-like weak inducer of apoptosis(sTWEAK)in ...Objective To study the association between early growth of haematoma with biomarkers of endothelial dysfunction such as leukoaraiosis(LA)and the soluble tumour necrosis factor-like weak inducer of apoptosis(sTWEAK)in patients with intracerebral haemorrhage(ICH).Methods This is a retrospective observational study of patients with nontraumatic ICH.Clinical and biochemical parameters were analysed.sTWEAK levels were measured by ELISA.LA was analysed in the hemisphere without haemorrhage to avoid interference with the acute injury.The main endpoint was the haematoma growth evaluated by the difference in volume between the second and the initial neuroimage.Poor functional outcome,defined as a modified Rankin Scale>2 at 3 months,was considered as secondary endpoint.Receiver operating characteristic curve analysis was performed to stablish the best cut-off for sTWEAK levels associated with haematoma growth.Results We included 653 patients with ICH in our analysis(71.1±11.9 years,44%women).Haematoma growth was observed in 188 patients(28.8%).sTWEAK levels≥5600 pg/mL predicted ICH growth with a sensitivity of 84%and a specificity of 87%.sTWEAK levels≥5600 pg/mL and the presence of LA were associated with haematoma growth(OR:42.46;(CI 95%22.67 to 79.52)and OR:2.73(CI 95%1.39 to 5.34),respectively).Also,the presence of LA(OR:4.31(CI 95%2.89 to 6.42))and the interaction between ICH growth and sTWEAK(OR:2.23(CI 95%1.40 to 3.55))were associated with poor functional outcome at 3 months.Conclusion sTWEAKs,together with the presence and grade of LA,are biomarkers able to predict ICH growth and poor functional outcome in patients with ICH.展开更多
Background Alzheimer’s disease(AD)exhibits mitochondrial dysfunctions associated with dysregulated metabolism,brain inflammation,synaptic loss,and neuronal cell death.As a key protein serving as the mitochondrial gat...Background Alzheimer’s disease(AD)exhibits mitochondrial dysfunctions associated with dysregulated metabolism,brain inflammation,synaptic loss,and neuronal cell death.As a key protein serving as the mitochondrial gatekeeper,the voltage-dependent anion channel-1(VDAC1)that controls metabolism and Ca2+homeostasis is positioned at a convergence point for various cell survival and death signals.Here,we targeted VDAC1 with VBIT-4,a newly developed inhibitor of VDAC1 that prevents its pro-apoptotic activity,and mitochondria dysfunction.Methods To address the multiple pathways involved in AD,neuronal cultures and a 5×FAD mouse model of AD were treated with VBIT-4.We addressed multiple topics related to the disease and its molecular mechanisms using immunoblotting,immunofluorescence,q-RT-PCR,3-D structural analysis and several behavioral tests.Results In neuronal cultures,amyloid-beta(Aβ)-induced VDAC1 and p53 overexpression and apoptotic cell death were prevented by VBIT-4.Using an AD-like 5×FAD mouse model,we showed that VDAC1 was overexpressed in neurons surrounding Aβplaques,but not in astrocytes and microglia,and this was associated with neuronal cell death.VBIT-4 prevented the associated pathophysiological changes including neuronal cell death,neuroinflammation,and neuro-metabolic dysfunctions.VBIT-4 also switched astrocytes and microglia from being pro-inflammatory/neurotoxic to neuroprotective phenotype.Moreover,VBIT-4 prevented cognitive decline in the 5×FAD mice as evaluated using several behavioral assessments of cognitive function.Interestingly,VBIT-4 protected against AD pathology,with no significant change in phosphorylated Tau and only a slight decrease in Aβ-plaque load.Conclusions The study suggests that mitochondrial dysfunction with its gatekeeper VDAC1 is a promising target for AD therapeutic intervention,and VBIT-4 is a promising drug candidate for AD treatment.展开更多
基金partially supported by grants from the Xunta de Galicia(IN607A2018/3 to TS,IN607D 2020/09 to TS,IN606A-2021/015 to ACIN606B-2021/010 to DRS)+3 种基金Science Ministry of Spain(RTI2018-102165-B-I00 to TS,RTC2019007373-1 to TS)supported by grants from the INTERREG Atlantic Area(EAPA_791/2018_NEUROATLANTIC project to TS)INTER-REG V A España Portugal(POCTEP)(0624_2IQBIONEURO_6_E to TS)the European Regional Development Fund(ERDF)。
文摘Alzheimer’s disease(AD)is the main neurodegenerative disease leading to dementia and cognitive impairment in the elderly.Considering AD to be an epidemic,an increase from the current 50 million to more than 150 million patients is expected by the year 2050.
基金supported by grants from the Spanish Ministry of Economy and Competitiveness(SAF2014-56336)the Instituto de Salud Carlos III(PI13/00292&PI14/01879)+5 种基金the Spanish Research Network on Cerebrovascular Diseases(RETICS INVICTUSRD12/0014)the Xunta de Galicia(Department of Education,GRC2014/027)the European Union program FEDERF.Campos(CP14/00154)TS(CP12/03121)are recipients of a research contract from Miguel Servet Program of Instituto de Salud Carlos III
文摘Intracerebral hemorrhage (ICH) is the most severe cerebrovascular disease, which represents a leading cause of death and disability in developed countries. However, therapeutic options are limited, so is mandatory to investigate repairing processes after stroke in order to develop new therapeutic strategies able to promote brain repair processes. Therapeutic angiogenesis and vasculogenesis hold promise to improve outcome of ICH patients. In this regard, circulating endothelial progenitor cells (EPCs) have recently been suggested to be a marker of vascular risk and endothelial function. Moreover, EPC levels have been associated with good neurological and functional outcome as well as reduced residual hematoma volume in ICH patients. Finally, experimental and clinical studies indicate that EPC might mediate endothelial cell regeneration and neovascularization. Therefore, EPC-based therapy could be an excellent therapeutic option in ICH. In this mini-review, we discuss the present status of knowledge about the possible therapeutic role of EPCs in ICH, molecular mechanisms, and the future perspectives and strategies for their use in clinical practice.
基金supported by Instituto de Salud Carlos III(PI17/01103)Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS PLUS(RD16/0019)+1 种基金Spanish Ministry ofEconomy and Competitiveness(SAF2017-84267-R)Xunta de Galicia(Consellería Educación:GRC2014/027 and IN607A2018/3)
文摘Epidemiology and physiopathology of ischemic stroke:Every year, around 15 million of people suffer a stroke event all around the world. Among those, around 6.7 million will die, and most of the survivors will suffer some grade of disability.
文摘Correction:Translational Neurodegeneration(2022)11:58 https://doi.org/10.1186/s40035-022-00329-7 Following publication of this article[1],the authors iden-tified an error in the family name of Alon Monsonego.The incorrect author name is:Alon Monsengo.The correct author name is:Alon Monsonego.The author group has been updated above and the orig-inal article[1]has been corrected.
基金This study was partially supported by grants from the Spanish Ministry of Science and Innovation(SAF2017-84267-R)Xunta de Galicia(Axencia Galega de Innovación(GAIN):IN607A2018/3)+2 种基金Instituto de Salud Carlos III(ISCIII)(PI17/00540,PI17/01103)Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS PLUS(RD16/0019)by the European Union FEDER program.T.Sobrino(CPII17/00027),F.Campos(CPII19/00020)are recipients of research contracts from the Miguel Servet Program(Instituto de Salud Carlos III).
文摘Objective To study the association between early growth of haematoma with biomarkers of endothelial dysfunction such as leukoaraiosis(LA)and the soluble tumour necrosis factor-like weak inducer of apoptosis(sTWEAK)in patients with intracerebral haemorrhage(ICH).Methods This is a retrospective observational study of patients with nontraumatic ICH.Clinical and biochemical parameters were analysed.sTWEAK levels were measured by ELISA.LA was analysed in the hemisphere without haemorrhage to avoid interference with the acute injury.The main endpoint was the haematoma growth evaluated by the difference in volume between the second and the initial neuroimage.Poor functional outcome,defined as a modified Rankin Scale>2 at 3 months,was considered as secondary endpoint.Receiver operating characteristic curve analysis was performed to stablish the best cut-off for sTWEAK levels associated with haematoma growth.Results We included 653 patients with ICH in our analysis(71.1±11.9 years,44%women).Haematoma growth was observed in 188 patients(28.8%).sTWEAK levels≥5600 pg/mL predicted ICH growth with a sensitivity of 84%and a specificity of 87%.sTWEAK levels≥5600 pg/mL and the presence of LA were associated with haematoma growth(OR:42.46;(CI 95%22.67 to 79.52)and OR:2.73(CI 95%1.39 to 5.34),respectively).Also,the presence of LA(OR:4.31(CI 95%2.89 to 6.42))and the interaction between ICH growth and sTWEAK(OR:2.23(CI 95%1.40 to 3.55))were associated with poor functional outcome at 3 months.Conclusion sTWEAKs,together with the presence and grade of LA,are biomarkers able to predict ICH growth and poor functional outcome in patients with ICH.
基金The Israel Science Foundation,Grant No.974/19,and by a grant from the National Institute for Biotechnology in the Negev(NIBN)to VSB.
文摘Background Alzheimer’s disease(AD)exhibits mitochondrial dysfunctions associated with dysregulated metabolism,brain inflammation,synaptic loss,and neuronal cell death.As a key protein serving as the mitochondrial gatekeeper,the voltage-dependent anion channel-1(VDAC1)that controls metabolism and Ca2+homeostasis is positioned at a convergence point for various cell survival and death signals.Here,we targeted VDAC1 with VBIT-4,a newly developed inhibitor of VDAC1 that prevents its pro-apoptotic activity,and mitochondria dysfunction.Methods To address the multiple pathways involved in AD,neuronal cultures and a 5×FAD mouse model of AD were treated with VBIT-4.We addressed multiple topics related to the disease and its molecular mechanisms using immunoblotting,immunofluorescence,q-RT-PCR,3-D structural analysis and several behavioral tests.Results In neuronal cultures,amyloid-beta(Aβ)-induced VDAC1 and p53 overexpression and apoptotic cell death were prevented by VBIT-4.Using an AD-like 5×FAD mouse model,we showed that VDAC1 was overexpressed in neurons surrounding Aβplaques,but not in astrocytes and microglia,and this was associated with neuronal cell death.VBIT-4 prevented the associated pathophysiological changes including neuronal cell death,neuroinflammation,and neuro-metabolic dysfunctions.VBIT-4 also switched astrocytes and microglia from being pro-inflammatory/neurotoxic to neuroprotective phenotype.Moreover,VBIT-4 prevented cognitive decline in the 5×FAD mice as evaluated using several behavioral assessments of cognitive function.Interestingly,VBIT-4 protected against AD pathology,with no significant change in phosphorylated Tau and only a slight decrease in Aβ-plaque load.Conclusions The study suggests that mitochondrial dysfunction with its gatekeeper VDAC1 is a promising target for AD therapeutic intervention,and VBIT-4 is a promising drug candidate for AD treatment.