Activated microglial cells synthesize and secrete AGE-albumin

Byun, Kyunghee; Bayarsaikhan, Enkhjaigal; Kim, Daesik; Son, Myeongjoo; Hong, Jihyung; Jeong, Goo‐Bo; Paek, Sun Ha; Won, Moo‐Ho; Lee, Bong-Hee

doi:10.5115/acb.2012.45.1.47

Cited by 26 publications

(21 citation statements)

References 12 publications

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“…Finally, it is worth reporting that it has recently been shown that glial cells in the CNS can produce albumin [7,[38][39][40], but how much this contributes to the total CSF albumin concentration is still being debated. QAlb, therefore, still remains the only validated laboratory tool for assessing B-CSF-B permeability.…”

Section: Discussionmentioning

confidence: 99%

Increased age and male sex are independently associated with higher frequency of blood–cerebrospinal fluid barrier dysfunction using the albumin quotient

Castellazzi

Morotti²,

Tamborino

et al. 2020

Fluids Barriers CNS

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Background: The cerebrospinal fluid (CSF)/serum quotient of albumin (QAlb) is the most used biomarker for the evaluation of blood-cerebrospinal fluid barrier (B-CSF-B) permeability. For years QAlb was considered only as an age-related parameter but recently it has also been associated to sex. The aim of the present study was to explore the impact of sex in the determination of B-CSF-B dysfunction. Methods: The analysis was retrospectively conducted on subjects consecutively admitted to the neurological ward. CSF and serum albumin levels were measured by immunonephelometry and pathological QAlb thresholds were considered: 6.5 under 40 years, 8.0 in the age 40-60 and 9.0 over 60 years. Results: 1209 subjects were included in the study. 718 females and 491 males (age: 15-88 years): 24.6% of patients had a diagnosis of multiple sclerosis, 23.2% suffered from other inflammatory neurological diseases, 24.6% were affected by non-inflammatory neurological diseases, and for 27.6% of patients the final neurological diagnosis could not be traced. Dysfunctional B-CSF-B was detected more frequently (44 vs. 20.1%, p < 0.0001) and median QAlb value were higher (7.18 vs. 4.87, p < 0.0001) in males than in females in the overall study population and in all disease subgroups. QAlb and age were positively correlated both in female (p < 0.0001) and male (p < 0.0001) patients, however the slopes of the two regression lines were not significantly different (p = 0.7149), while the difference between the elevations was extremely significant (p < 0.0001) with a gap of 2.2 units between the two sexes. Finally, in a multivariable linear regression analysis increased age and male sex were independently associated with higher QAlb in the overall study population (both p < 0.001) and after stratification by age and disease group. Conclusions: Accordingly, identification and validation of sex-targeted QAlb thresholds should be considered as a novel tool in an effort to achieve more precision in the medical approach.

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Section: Discussionmentioning

confidence: 99%

Increased age and male sex are independently associated with higher frequency of blood–cerebrospinal fluid barrier dysfunction using the albumin quotient

Castellazzi

Morotti²,

Tamborino

et al. 2020

Fluids Barriers CNS

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“…These results are also similar with those for AD and alcoholic brains. [21][22][23] Next, we investigated whether AGE-albumin is key for inducing dopaminergic neuronal death in LUMHES cells. The International Journal of Nanomedicine is an international, peerreviewed journal focusing on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study demonstrated that only AGE-albumin has microglia-specific expression in pathological conditions such as AD. [20][21][22] To determine the AGE-albumin synthesis and secretion in activated microglial cells, we evaluated whether AGE-albumin synthesis and secretion are elevated by α-synuclein ( Figure 3A). After α-synuclein exposure, human microglial cells showed significant elevation of AGE-albumin.…”

Section: Activated Microglial Cells Synthesize and Secrete Age-albuminmentioning

confidence: 99%

“…[16][17][18][19] We recently reported that human microglial cells synthesize and secrete advanced glycation end product-albumin (AGE-albumin) in AD, and AGE-albumin is one of the possible inducers of neuronal death through an increase in the receptor to AGE (RAGE) in humans and animals. [20][21][22][23] The pathophysiology of PD brain damage is also highly associated with inflammation through microglial activation. Accumulated AGE-albumin from activated microglial cells continuously induces neuronal RAGE-albumin, resulting in DA neuronal death.…”

Section: Introductionmentioning

confidence: 99%

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Microglial AGE-albumin is critical for neuronal death in Parkinson's disease: a possible implication for theranostics

Bayarsaikhan

Lee

et al. 2016

IJN

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Advanced glycation end products (AGEs) are known to play an important role in the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD), by inducing protein aggregation and cross-link, formation of Lewy body, and neuronal death. In this study, we observed that AGE-albumin, the most abundant AGE product in the human PD brain, is synthesized in activated microglial cells and accumulates in the extracellular space. AGE-albumin synthesis in human-activated microglial cells is distinctly inhibited by ascorbic acid and cytochalasin treatment. Accumulated AGE-albumin upregulates the receptor to AGE, leading to apoptosis of human primary dopamine (DA) neurons. In animal experiments, we observed reduced DA neuronal cell death by treatment with soluble receptor to AGE. Our study provides evidence that activated microglial cells are one of the main contributors in AGE-albumin accumulation, deleterious to DA neurons in human and animal PD brains. Finally, activated microglial AGE-albumin could be used as a diagnostic and therapeutic biomarker with high sensitivity for neurodegenerative disorders, including PD.

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“…Activation of AGE receptors (RAGE) increases ROS formation and leads to activation of NF-κB pathway. This ultimately promotes the expression of a variety of pro-inflammatory mediators [2,122,130,131] thus adjuvanting/strengthening the immune and pro-inflammatory responses. In fact increased accumulation of AGEs in Alzheimer’s patients has proven to cause neuronal death and degeneration, thereby supporting the fact that diabetes increases the risk of AD and any shift in normal glucose metabolism is deleterious for BBB integrity.…”

Section: Oxidative Stress At Bbb In Dmmentioning

confidence: 99%

Diabetes Mellitus and Blood-Brain Barrier Dysfunction: An Overview

Prasad

Sajja

Naik

et al. 2014

J Pharmacovigilance

151

106

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A host of diabetes-related insults to the central nervous system (CNS) have been clearly documented in type-1 and -2 diabetic patients as well as experimental animal models. These host of neurological disorders encompass hemodynamic impairments (e.g., stroke), vascular dementia, cognitive deficits (mild to moderate), as well as a number of neurochemical, electrophysiological and behavioral alterations. The underlying causes of diabetes-induced CNS complications are multifactorial and are relatively little understood although it is now evident that blood-brain barrier (BBB) damage plays a significant role in diabetes-dependent CNS disorders. Changes in plasma glucose levels (hyper- or hypoglycemia) have been associated with altered BBB transport functions (e.g., glucose, insulin, choline, amino acids, etc.), integrity (tight junction disruption), and oxidative stress in the CNS microcapillaries. Last two implicating a potential causal role for upregulation and activation of the receptor for advanced glycation end products (RAGE). This type I membrane-protein also transports amyloid-beta (Aβ) from the blood into the brain across the BBB thus, establishing a link between type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD, also referred to as “type 3 diabetes”). Hyperglycemia has been associated with progression of cerebral ischemia and the consequent enhancement of secondary brain injury. Difficulty in detecting vascular impairments in the large, heterogeneous brain microvascular bed and dissecting out the impact of hyper- and hypoglycemia in vivo has led to controversial results especially with regard to the effects of diabetes on BBB. In this article, we review the major findings and current knowledge with regard to the impact of diabetes on BBB integrity and function as well as specific brain microvascular effects of hyper- and hypoglycemia.

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Activated microglial cells synthesize and secrete AGE-albumin

Cited by 26 publications

References 12 publications

Increased age and male sex are independently associated with higher frequency of blood–cerebrospinal fluid barrier dysfunction using the albumin quotient

Increased age and male sex are independently associated with higher frequency of blood–cerebrospinal fluid barrier dysfunction using the albumin quotient

Microglial AGE-albumin is critical for neuronal death in Parkinson's disease: a possible implication for theranostics

Diabetes Mellitus and Blood-Brain Barrier Dysfunction: An Overview

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Activated microglial cells synthesize and secrete AGE-albumin

Cited by 26 publications

References 12 publications

Increased age and male sex are independently associated with higher frequency of blood–cerebrospinal fluid barrier dysfunction using the albumin quotient

Increased age and male sex are independently associated with higher frequency of blood–cerebrospinal fluid barrier dysfunction using the albumin quotient

Microglial AGE-albumin is critical for neuronal death in Parkinson&#39;s disease: a possible implication for theranostics

Diabetes Mellitus and Blood-Brain Barrier Dysfunction: An Overview

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Microglial AGE-albumin is critical for neuronal death in Parkinson's disease: a possible implication for theranostics