RANTES upregulation in the Alzheimer's disease brain: A possible neuroprotective role

Tripathy, Debjani; Thirumangalakudi, Lakshmi; Grammas, Paula

doi:10.1016/j.neurobiolaging.2008.03.009

Cited by 135 publications

(110 citation statements)

References 45 publications

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“…Of these secreted products, some were found to be neurotoxic (e.g., thrombin) and others neuroprotective (endothelin-1, and CCL5/RANTES). [176][177][178] However, an overall neurotoxic effect was observed after neuronal coculture with AD microvessels or conditioned medium. 179 Recent work by the same group has suggested that vascular endothelial growth factor (VEGF) may contribute to AD neurodegeneration.…”

Section: Neuronsmentioning

confidence: 99%

Blood–Brain Barrier Dysfunction as a Cause and Consequence of Alzheimer's Disease

Erickson

Banks

2013

J Cereb Blood Flow Metab

476

363

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The blood-brain barrier (BBB) plays critical roles in the maintenance of central nervous system (CNS) homeostasis. Dysfunction of the BBB occurs in a number of CNS diseases, including Alzheimer's disease (AD). A prevailing hypothesis in the AD field is the amyloid cascade hypothesis that states that amyloid-b (Ab) deposition in the CNS initiates a cascade of molecular events that cause neurodegeneration, leading to AD onset and progression. In this review, the participation of the BBB in the amyloid cascade and in other mechanisms of AD neurodegeneration will be discussed. We will specifically focus on three aspects of BBB dysfunction: disruption, perturbation of transporters, and secretion of neurotoxic substances by the BBB. We will also discuss the interaction of the BBB with components of the neurovascular unit in relation to AD and the potential contribution of AD risk factors to aspects of BBB dysfunction. From the results discussed herein, we conclude that BBB dysfunction contributes to AD through a number of mechanisms that could be initiated in the presence or absence of Ab pathology. Keywords: Alzheimer's disease; blood-brain barrier; cerebrospinal fluid; diabetes; inflammation; neurovascular unit INTRODUCTION Alzheimer's disease (AD) is the most common type of dementia, and affects B36 million individuals worldwide (http://www.alz. co.uk/research/world-report). The majority of individuals afflicted with AD initially present with symptoms of memory loss and cognitive impairment late in life (Z65 years old). These symptoms increase in severity as AD progresses, often become so debilitating that institutionalization is necessary, and are eventually fatal. Therefore, AD is a disease with tremendous socioeconomic cost. Because of the growing aged population and lack of treatments that can prevent or slow disease progression, future AD prevalence is expected to increase to an extent that it may threaten the sustainability of healthcare systems worldwide. This necessitates a global effort to better understand AD, with the goal of developing treatments that can prevent or slow AD progression. Journal of Cerebral BloodMuch of the focus in AD research has been on amyloid-b peptide (Ab) and tau, which are the protein constituents of the hallmark senile plaques and neurofibrillary tangles that pathologically define AD. The amyloid cascade hypothesis, initially proposed by Hardy and Higgins in 1992, 1 updated by Hardy and Selkoe in 2002, 2 and still a prevalent focus of AD research today, states that deposition of Ab in the brain is the initiating event in AD. Although the hypothesis remains generally accepted, it is also increasingly evident that Ab plays a complex, multifaceted role in AD progression. In rare, familial forms of AD, mutations in the Ab precursor protein (APP) or in presenilin proteins, the enzymes that cleave Ab from APP, cause increased Ab deposition. In the remainder of AD cases, it is thought that Ab deposition results from deficient clearance. 2 Multiple routes of clearance have been elucidat...

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Section: Neuronsmentioning

confidence: 99%

Blood–Brain Barrier Dysfunction as a Cause and Consequence of Alzheimer's Disease

Erickson

Banks

2013

J Cereb Blood Flow Metab

476

363

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“…The cytokine encoded by this gene functions as a chemo-attractant for blood monocytes, memory T-helper cells and eosinophils. It has been found that CCL5 levels are up-regulated in microglia and cerebrovascular tissue in the first phase after exposure to amyloid (12,13), while after a longer period of exposure a decrease of CCL5 was shown (14). Furthermore, CCL5 has been associated with the prevention of amyloid associated cell death (15).…”

Section: Discussionmentioning

confidence: 99%

Decreased mRNA expression of CCL5 [RANTES] in Alzheimer's disease blood samples

Kester

Flier²,

Visser³

et al. 2012

Clinical Chemistry and Laboratory Medicine

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Background: A recent study reported that an 18-analyte multiplexed plasma panel of signaling proteins differentiated Alzheimer's disease (AD) from controls. This study measured mRNA expression for nine of these promising biomarkers in 23 AD patients and 23 age-and sex-matched controls. Methods: Total RNA was isolated from PaxGene RNA tubes. Relative mRNA expression levels of CCL5 wRANTESx, CSF1, ICAM1, IGFBP6, IL1A, IL3, IL8, PDGFB and TNF were determined by Q-RT-PCR, with GAPDH as housekeeping gene. Results: A panel of five markers (CCL5, CSF1, ICAM1, IL8, TNF) with detectable expression levels in all individuals differed between AD patients and controls (p interaction -0.10). Especially, the relative expression level of CCL5 was lower in AD patients than in controls (p-0.005). Across groups, levels of both CCL5 and TNF were correlated to CSF levels of t (rs0.39, rs0.32), pt-181 (rs0.38, rs0.33), and MMSE (rs-0.31, rs-0.33, all p-0.05). Conclusions: The measured panel, and especially CCL5, could aid in the differentiation of AD from controls.

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“…52 The RANTES protein, as well as several other chemokines in astrocytes, is upregulated as a response to a cytokine-mediated increase of ROS. 53 Moreover, oxidative stress upregulates RANTES protein expression in endothelial cells in the brain.…”

Section: C-c Motif Ligandmentioning

confidence: 99%

“…53 Moreover, oxidative stress upregulates RANTES protein expression in endothelial cells in the brain. 52 In brain injury models, elevated levels of the RANTES protein contributed to immune cell recruitment that occurred concurrently with increased rates of neuronal death. 52,54,55 C-X-C Motif Ligand 8 CXCL8 (IL-8) is a microglia-derived chemokine that is produced in response to pro-inflammatory signals such as Aβ.…”

Section: C-c Motif Ligandmentioning

confidence: 99%