Role of Fibrinogen in Alzheimer's Disease
Role of Fibrinogen in Alzheimer's Disease
批准号:
10737135
负责人:
ERIN H NORRIS
金额:
$77.37万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
未结题
起止时间:
2018-04-01 至 2028-07-31
关键词:
AffectAffinityAlzheimer&aposs DiseaseAlzheimer&aposs disease modelAlzheimer&aposs disease pathologyAlzheimer&aposs disease patientAmyloid beta-42Amyloid beta-ProteinBindingBlood ProteinsBlood coagulationBlood flowBrainBrain PathologyCell CommunicationCellsCoagulation ProcessComplexCulture TechniquesCytolysisDiseaseElementsFibrinFibrinogenFunctional disorderGoalsHippocampusHumanImaging TechniquesImpaired cognitionIn VitroInflammationInjectionsMeasuresMolecularMusNerve DegenerationNeuronal DysfunctionPathogenesisPathogenicityPathway interactionsPeptidesPhysiologicalPopulation DynamicsPropertyProteinsProtocols documentationResistanceRoleSamplingSeverity of illnessSliceStructureSynapsesSystemToxic effectVariantVascular DiseasesVascular Systemabeta toxicitybiophysical propertiesbiophysical techniquesimprovedin vivomouse modelmutantnegative affectneuroinflammationneuron lossnovelnovel diagnosticsnovel therapeuticspharmacologicprotective effectprotein purificationsingle nucleus RNA-sequencingsmall moleculevascular contributions
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
Alzheimer's disease (AD) is a multifactorial disorder with many pathogenic elements. One contributing factor is
vascular dysfunction, which can be both a result of the primary AD pathogenesis and a cause of neuronal loss
and subsequent cognitive impairment. The molecular mechanisms by which AD and the vascular system
intersect and influence each other are still unclear. We have been working for two decades to try to better
define this molecular interaction.
We have shown that beta amyloid (Aβ), the peptide that is a driver of AD, interacts with fibrinogen and
increases blood clot formation. These clots have an altered structure and are resistant to lysis. These
abnormal clots can contribute to reduced blood flow and increased inflammation, both of which could
contribute to vascular contributions to AD.
We have now found that the Aβ/fibrinogen complexes can have toxic effects independent of clotting. In
hippocampal slice cultures, Aβ/fibrinogen complexes are more toxic than either Aβ or fibrinogen alone. These
results identify a new mechanism by which the interaction of Aβ and fibrinogen can lead to neuronal
dysfunction.
Mutant and longer forms of Aβ are sometimes much more toxic that the classical Aβ42 and Aβ40 species. We
show that some mutant forms of Aβ that are more toxic interact much more strongly with fibrinogen. These Aβ
variants provide an entrée for studying the mechanisms by which Aβ/fibrinogen complexes are toxic in AD.
Therefore, our main goal is to explore the cellular and molecular mechanisms by which Aβ variants and their
fibrinogen complexes negatively affect the brain.
期刊论文(16)
专著(0)
科研奖励(0)
会议论文
登录
查看更多内容
DOI:
10.3390/ijms24087046
发表时间:
2023-04-11
期刊:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
影响因子:
5.6
作者:
[Badimon, Ana, Torrente, Daniel, Norris, Erin H.]
通讯作者:
Norris, Erin H.
DOI:
10.1002/trc2.12173
发表时间:
2021
期刊:
Alzheimer's & dementia (New York, N. Y.)
影响因子:
--
作者:
[Amelianchik A, Merkel J, Palanisamy P, Kaneki S, Hyatt E, Norris EH]
通讯作者:
Norris EH
DOI:
10.1016/j.neurobiolaging.2021.07.015
发表时间:
2021-11
期刊:
Neurobiology of aging
影响因子:
4.2
作者:
[Tataryn NM, Singh V, Dyke JP, Berk-Rauch HE, Clausen DM, Aronowitz E, Norris EH, Strickland S, Ahn HJ]
通讯作者:
Ahn HJ
DOI:
10.1002/rth2.12504
发表时间:
2021-05
期刊:
Research and practice in thrombosis and haemostasis
影响因子:
4.6
作者:
[Singh PK, Badimon A, Chen ZL, Strickland S, Norris EH]
通讯作者:
Norris EH
DOI:
10.3389/fnagi.2023.1064178
发表时间:
2023
期刊:
Frontiers in aging neuroscience
影响因子:
4.8
作者:
[]
通讯作者:
共 7 条
Anti-high molecular weight kininogen antibody for Alzheimer's disease diagnosis and therapy
-
批准号:10097427
-
项目类别:
-
资助金额:$175.09万
-
财政年份:2020
-
负责人:ERIN H NORRIS
-
依托单位:
Role of the Contact System in Alzheimer's Disease
-
批准号:10112965
-
项目类别:
-
资助金额:$54.63万
-
财政年份:2018
-
负责人:ERIN H NORRIS
-
依托单位:
Role of the Contact System in Alzheimer's Disease
-
批准号:10328951
-
项目类别:
-
资助金额:$54.63万
-
财政年份:2018
-
负责人:ERIN H NORRIS
-
依托单位:
Role of fibrinogen in Alzheimer's disease
-
批准号:10297855
-
项目类别:
-
资助金额:$54.41万
-
财政年份:2018
-
负责人:ERIN H NORRIS
-
依托单位:
Role of fibrinogen in Alzheimer's disease
-
批准号:10054200
-
项目类别:
-
资助金额:$54.41万
-
财政年份:2018
-
负责人:ERIN H NORRIS
-
依托单位:
海外基金