Scavenger receptor class B type I (SR-BI) regulates perivascular macrophages and modifies amyloid pathology in an Alzheimer mouse model

Thanopoulou, Kalliopi; Fragkouli, Apostolia; Stylianopoulou, Fotini; Georgopoulos, Spiros

doi:10.1073/pnas.1005888107

Cited by 119 publications

(120 citation statements)

References 42 publications

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“…Microglia are intimately associated with Ab plaques in AD, but not with the diffuse Ab plaques characteristic of aging (249,262,287,669,672). The trigger for activation in AD is unclear, but the invasion of plaques by morphologically active microglia is seen in AD transgenic mice models, as well as when Ab is injected into the brain of otherwise healthy mice or in in vitro experiments (9,462,528,635,672). Multiple receptors have been reported to mediate this process: for instance, the receptor for advanced glycation end products (RAGE) (706), scavenger receptors (9,123,635), the G-protein-coupled chemo-attractant receptor (341), the formylpeptide receptor 2 (262), and toll like receptors (528).…”

Section: Microglia Astrocytes and Oxidative Stressmentioning

confidence: 97%

Alzheimer's Disease: Redox Dysregulation As a Common Denominator for Diverse Pathogenic Mechanisms

Bernhardi

Eugenı́n

2012

Antioxidants & Redox Signaling

156

113

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Alzheimer's disease (AD) is the most common cause of dementia and a progressive neurodegeneration that appears to result from multiple pathogenic mechanisms (including protein misfolding/aggregation, involved in both amyloid β-dependent senile plaques and tau-dependent neurofibrillary tangles), metabolic and mitochondrial dysfunction, excitoxicity, calcium handling impairment, glial cell dysfunction, neuroinflammation, and oxidative stress. Oxidative stress, which could be secondary to several of the other pathophysiological mechanisms, appears to be a major determinant of the pathogenesis and progression of AD. The identification of oxidized proteins common for mild cognitive impairment and AD suggests that key oxidation pathways are triggered early and are involved in the initial progression of the neurodegenerative process. Abundant data support that oxidative stress, also considered as a main factor for aging, the major risk factor for AD, can be a common key element capable of articulating the divergent nature of the proposed pathogenic factors. Pathogenic mechanisms influence each other at different levels. Evidence suggests that it will be difficult to define a single-target therapy resulting in the arrest of progression or the improvement of AD deterioration. Since oxidative stress is present from early stages of disease, it appears as one of the main targets to be included in a clinical trial. Exploring the articulation of AD pathogenic mechanisms by oxidative stress will provide clues for better understanding the pathogenesis and progression of this dementing disorder and for the development of effective therapies to treat this disease.

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Section: Microglia Astrocytes and Oxidative Stressmentioning

confidence: 97%

Alzheimer's Disease: Redox Dysregulation As a Common Denominator for Diverse Pathogenic Mechanisms

Bernhardi

Eugenı́n

2012

Antioxidants & Redox Signaling

156

113

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“…In brain, they are distinct from other perivascular cells and microglia for their morphology, immune phenotype, and propensity to phagocytosis (18,25). Brain PVMs are thought to be beneficial in models of Alzheimer disease by removing amyloid-β peptides from the perivascular space and preventing amyloid accumulation in cerebral blood vessels (amyloid angiopathy) (48,49). On the other hand, hypothalamic neurohumoral signaling by PVMs across the BBB may be deleterious by promoting inflammation and sympathetic activation in models of fever or myocardial infarction, respectively (28,29), and may contribute to hypertensive cerebrovascular remodeling (50).…”

Section: Nox2 Deletion In Bm Cells (Nox2 -/-mentioning

confidence: 99%

Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension

Faraco¹,

Sugiyama²,

Lane³

et al. 2016

Journal of Clinical Investigation

251

358

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In this study we investigated the contribution of PVMs to the neurovascular and cognitive dysfunction induced by hypertension. We found that depletion of PVMs in models of chronic hypertension suppresses vascular oxidative stress and ameliorates the attendant impairment in neurovascular coupling and endothelium-dependent responses. Studies in bone marrow (BM) chimeras provided evidence that the dysfunction is mediated by ANGII acting on PVM AT1Rs resulting in NOX2-dependent ROS production. Importantly, concomitant to the neurovascular improvement, PVM depletion also rescued cognitive dysfunction. The findings unveil a previously unrecognized role of PVMs in the neurovascular and cognitive dysfunction induced by hypertension, and identify PVMs as a novel pathogenic component of the NVU of critical importance for brain health.

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“…193,194) Reduction of SR-BI in a mouse model of AD (J20) induced a deterioration in learning and memory and promoted cerebral amyloid angiopathy as well as the deposition of fibrillar Ab in the hippocampus. 195) In addition, aged SR-BI knockout mice (over 20 months old) revealed an impairment of long-term potentiation in the hippocampus and deficits of recognition and spatial memories. 196) The CSF contains the phospholipid transfer protein (PLTP), which has been proposed to facilitate the transport of phospholipid for generation of mature lipoproteins.…”

Section: Lipid Metabolism and Admentioning

confidence: 99%

Lipid Metabolism and Glial Lipoproteins in the Central Nervous System

Hayashi

2011

Biological & Pharmaceutical Bulletin

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INTRODUCTIONFunctions of the central nervous system (CNS) are performed mainly by neurons and glia-primarily astrocytes, microglia and oligodendrocytes. It has been thought for a long time that glia only passively support neurons, but we now know that glia actively attend to assist in neuronal functions like synaptogenesis and neurotransmission. 1) Although it was believed that ca. 90% of the cells in the brain are glia and the rest of cells are neurons, Azevedo et al. recently reported that the numbers of neurons and non-neuronal cells (glia) are close to equal in human adult brain.2) Brain is the most cholesterol-rich organ in the body, and cholesterol metabolism in the CNS is tightly regulated between neurons and glia. [3][4][5][6][7] Imbalances in the metabolism of lipids, especially cholesterol, are closely linked to the development of several neurodegenerative disorders such as Alzheimer's disease, 8,9) Niemann-Pick type C disease 10) and Smith-Lemli Opitz syndrome. 11,12) In this review the regulation of lipid metabolism and the roles of glial lipoproteins in the CNS will be discussed. LIPID HOMEOSTASIS IN THE CNSThe system of lipid metabolism and transport in the CNS is different from that in peripheral tissues because the CNS is segregated from the peripheral circulation by the blood-brain barrier (BBB).13) Although lipoprotein particles can cross the BBB in vivo in Drosophila, which has a functional BBB like that in vertebrates, 14) lipoproteins in the mouse, rat and human do not cross the BBB. Consequently, since labeled cholesterol peripherally administrated was not found in the CNS of mammals, 15,16) cholesterol in the CNS is derived from de novo synthesis inside of the CNS. Furthermore, in the plasma of subjects who had liver transplantation the genotype of apolipoprotein (apo) E was that of the donor, whereas the subjects retained the own apo E genotype in the cerebrospinal fluid (CSF).17) Moreover, lipoproteins in the CNS consist of only high density lipoprotein (HDL)-like particles in contrast to the circulation which contains very low density lipoproteins (VLDL), low density lipoproteins (LDL) and HDL. It is known that the HDL-like particles in the CNS are secreted from glia (glial lipoproteins), mainly astrocytes and microglia, under normal conditions, [18][19][20] however lipoproteins can be secreted from neurons in vitro 21,22) and in vivo 23) under some specific conditions. Unesterified cholesterol is the major sterol in the adult brain, and small amounts of desmosterol and cholesteryl ester are also present. The majority (70-80%) of cholesterol in the adult brain is in myelin formed by oligodendrocytes. 24)Thus, the activity of cholesterol synthesis in the CNS is the highest during the myelinogenesis. After myelination, cholesterol synthesis continues at very low level in the CNS, and occurs mainly in astrocytes. 5,13,24) Neurons do not efficiently synthesize cholesterol and rely on external source of cholesterol from astrocytes, 25) so that neurons take up cholesterol as lipoproteins via ...

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Scavenger receptor class B type I (SR-BI) regulates perivascular macrophages and modifies amyloid pathology in an Alzheimer mouse model

Cited by 119 publications

References 42 publications

Alzheimer's Disease: Redox Dysregulation As a Common Denominator for Diverse Pathogenic Mechanisms

Alzheimer's Disease: Redox Dysregulation As a Common Denominator for Diverse Pathogenic Mechanisms

Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension

Lipid Metabolism and Glial Lipoproteins in the Central Nervous System

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