Dissecting the Crosstalk between Endothelial Mitochondrial Damage, Vascular Inflammation, and Neurodegeneration in Cerebral Amyloid Angiopathy and Alzheimer's Disease.
Dissecting the Crosstalk between Endothelial Mitochondrial Damage, Vascular Inflammation, and Neurodegeneration in Cerebral Amyloid Angiopathy and Alzheimer's Disease.
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DOI：
10.3390/cells10112903
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发表时间：
2021-10-27
期刊：
影响因子：
6
通讯作者：
Fossati S
中科院分区：
文献类型：
--
作者：
Parodi-Rullán RM;Javadov S;Fossati S
阿尔茨海默病 (AD) 是痴呆症最常见的病因，其病理学特征是存在由 β 淀粉样蛋白 (Aβ) 和过度磷酸化 tau 蛋白的神经元内神经原纤维缠结组成的实质老年斑。超过 80% 的 AD 患者和非痴呆个体的脑血管系统内也会出现 Aβ 积聚，这种情况称为脑淀粉样血管病 (CAA)。 CAA 的发展与神经血管功能障碍、血脑屏障 (BBB) 渗漏以及持续的血管和神经炎症有关，最终导致神经变性。尽管AD和CAA在病理学上是特征明确的疾病，但导致其发展的分子变化的时间顺序仍不清楚。大量证据表明，在 AD 和 CAA 的早期阶段，神经血管单元的各种细胞以及脑实质中的线粒体功能存在缺陷。功能失调的线粒体会释放危险相关分子模式（DAMP），激活多种炎症途径。在这篇综述中，我们收集证据来假设线粒体，特别是脑内皮细胞，作为 Aβ 诱导的血管炎症的传感器和引发剂的关键作用。激活的脉管系统将循环免疫细胞招募到脑实质中，导致 AD 和 CAA 中神经炎症和神经变性的发展。
Alzheimer’s disease (AD) is the most prevalent cause of dementia and is pathologically characterized by the presence of parenchymal senile plaques composed of amyloid β (Aβ) and intraneuronal neurofibrillary tangles of hyperphosphorylated tau protein. The accumulation of Aβ also occurs within the cerebral vasculature in over 80% of AD patients and in non-demented individuals, a condition called cerebral amyloid angiopathy (CAA). The development of CAA is associated with neurovascular dysfunction, blood–brain barrier (BBB) leakage, and persistent vascular- and neuro-inflammation, eventually leading to neurodegeneration. Although pathologically AD and CAA are well characterized diseases, the chronology of molecular changes that lead to their development is still unclear. Substantial evidence demonstrates defects in mitochondrial function in various cells of the neurovascular unit as well as in the brain parenchyma during the early stages of AD and CAA. Dysfunctional mitochondria release danger-associated molecular patterns (DAMPs) that activate a wide range of inflammatory pathways. In this review, we gather evidence to postulate a crucial role of the mitochondria, specifically of cerebral endothelial cells, as sensors and initiators of Aβ-induced vascular inflammation. The activated vasculature recruits circulating immune cells into the brain parenchyma, leading to the development of neuroinflammation and neurodegeneration in AD and CAA.
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影响因子：
7.4
作者：
Bergstraesser, Claudia;Hoeger, Simone;Rafat, Neysan
通讯作者：
Rafat, Neysan
影响因子：
4.8
作者：
Aldea, Roxana;Weller, Roy O.;Richardson, Giles
通讯作者：
Richardson, Giles
DOI：
10.1002/trc2.12145
发表时间：
2021
期刊：
Alzheimer's & dementia (New York, N. Y.)
影响因子：
--
作者：
Alakbarzade V;French JM;Howlett DR;Attems J;Francis PT;Stratton S;Clark CN;Pereira AC;Hainsworth AH
通讯作者：
Hainsworth AH
DOI：
10.1016/j.bbadis.2017.07.005
发表时间：
2018-01
期刊：
Biochimica et biophysica acta. Molecular basis of disease
影响因子：
--
作者：
Cabrera E;Mathews P;Mezhericher E;Beach TG;Deng J;Neubert TA;Rostagno A;Ghiso J
通讯作者：
Ghiso J
影响因子：
64.8
作者：
Baines, CP;Kaiser, RA;Molkentin, JD
通讯作者：
Molkentin, JD