Evidence for Altered LRP/RAGE Expression in Alzheimer Lesion Pathogenesis

Jeynes, Brian; Provias, John

doi:10.2174/156720508785908937

Cited by 82 publications

(65 citation statements)

References 24 publications

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“…83,84 Furthermore, RAGE upregulation is observed in the CNS microvasculature of humans with AD, as analyzed by histochemical methods in post-mortem tissue. 85,86 Systemic clearance of Ab is facilitated by the liver and, to a lesser extent, the kidneys and spleen. 55,87 Lipoprotein receptorrelated protein-1 was shown to be the predominant transporter that mediates clearance by the liver.…”

Section: Transport Of Amyloid-b Influx and Systemic Clearancementioning

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: Transport Of Amyloid-b Influx and Systemic Clearancementioning

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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“…One of the mechanisms in removing Aβ is mediated by liver and low-density lipoprotein receptorrelated protein (LRP-1) [8,9]. LRP-1 is a receptor for uptaking Aβ through hepatic [10].…”

Section: Introductionmentioning

confidence: 99%

Clearance of Amyloid Beta Plaques from Brain of Alzheimeric Rats by Lavandula angustifolia

Soheili¹,

Tavirani²,

Saifeddine³

2012

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An important marker in neurodegenerative Alzheimer's disease (AD) is abnormal production of amyloid beta (Aβ) peptide leading to formation of plaques in the brain. Through decreasing Aβ aggregates, anti-inflammatory agents, phagocytosis, and proteolytic enzymes are known to decline risk of Aβ plaque formation. In the previous study we showed that aqueous extract of Lavandula angustifolia (lavender), with known anti-inflammatory effects, improves memory deficits in animal model of Alzheimer. Here, we assess if lavender play a role in clearance of Aβ plaques in the hippocampus. The Alzheimeric animals were created with intracerebroventricular injection of Aβ 1-42. To confirm formation of Aβ plaques, brain sections were stained by Congo red method. Twenty days post-injection they were administered with different doses (50, 100 and 200 mg/kg) of the aqueous extract of lavender for duration of 20 days. Our results demonstrated that 50 mg/kg of lavender not effectively influenced the Aβ plaques. On the other hand, the herbal medicine at the doses of 100 and 200 mg/kg markedly decreased the extent of Aβ aggregates. We concluded that the lavender extract dose dependently underlies elimination of Aβ plaques. The exact mechanism by which the herbal medicine removes the Aβ aggregates needs to be elucidated.

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“…Показано, что при АБ продукты ПОЛ, в частности, 4-гидроксиноненаль (4-HNE), связываются в гиппокампе с LRP1, снижая его роль в качестве транспортного белка. Таким образом, у больных с АБ нарушается транспортная функция LRP1 [56]. Предполагают, что окисление LRP1 в крови является фактором риска для АБ [51].…”

Section: B-амилоид и его роль в генерации активных форм кислорода приunclassified

Oxidative stress and its effect on cells functional activity of Alzheimer's disease

et al. 2015

BIOMED KHIM

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The paper summarizes literature data on the importance of oxidative stress as one of the pathogenetic mechanisms in Alzheimer's disease. The paper describes the main specific and nonspecific ways of reactive oxygen species generation in the course of the disease development. The effect of reactive oxygen species generated by the functional activity of cells, i.e. apoptosis and mitotic cycle, is shown. The role of the regulatory system of nodal cells is performed by phosphorylation/dephosphorylation process which is associated with intense phosphorylation of tau protein and mitosis-specific proteins. In Alzheimer's disease, the regulating function of peptidyl-prolyl isomerases in particular of Pin1 associated with maintaining a balanced state of phosphorylation/dephosphorylation processes is disturbed. Taking into consideration the multifactorial impairment of the cell cycle control, this process should be considered from the standpoint of the general state of metabolic processes, and oxidative stress has one of the key positions in aging.

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Evidence for Altered LRP/RAGE Expression in Alzheimer Lesion Pathogenesis

Cited by 82 publications

References 24 publications

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

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

Clearance of Amyloid Beta Plaques from Brain of Alzheimeric Rats by Lavandula angustifolia

Oxidative stress and its effect on cells functional activity of Alzheimer's disease

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