scholarly journals Is Alzheimer's Associated Amyloid Beta an Innate Immune Protein

10.5772/63021 ◽  
2016 ◽  
Author(s):  
Ruth Kandel ◽  
Mitchell R. White ◽  
I-Ni Hseih ◽  
Kevan L. Hartshorn
Keyword(s):  
Amyloid Beta ◽  
Innate Immune

scholarly journals What Are the Molecular Mechanisms by Which Functional Bacterial Amyloids Influence Amyloid Beta Deposition and Neuroinflammation in Neurodegenerative Disorders?

2020 ◽  
Vol 21 (5) ◽  
pp. 1652 ◽  
Author(s):  
Robert P. Friedland ◽  
Joseph D. McMillan ◽  
Zimple Kurlawala
Keyword(s):  
Amyloid Beta ◽  
Neurodegenerative Disorders ◽  
Innate Immune System ◽  
Molecular Mechanisms ◽  
Innate Immune ◽  
Know How ◽  
Unique Distribution ◽  
The Brain

Despite the enormous literature documenting the importance of amyloid beta (Ab) protein in Alzheimer's disease, we do not know how Ab aggregation is initiated and why it has its unique distribution in the brain. In vivo and in vitro evidence has been developed to suggest that functional microbial amyloid proteins produced in the gut may cross-seed Ab aggregation and prime the innate immune system to have an enhanced and pathogenic response to neuronal amyloids. In this commentary, we summarize the molecular mechanisms by which the microbiota may initiate and sustain the pathogenic processes of neurodegeneration in aging.

scholarly journals Functional insights from biophysical study of TREM2 interactions with ApoE and Aβ1-42

2020 ◽  
Author(s):  
Daniel L. Kober ◽  
Melissa D. Stuchell-Brereton ◽  
Colin E. Kluender ◽  
Hunter B. Dean ◽  
Michael R. Strickland ◽  
...  
Keyword(s):  
Potential Function ◽  
Amyloid Beta ◽  
Hydrophobic Surface ◽  
Innate Immune ◽  
Potential Mechanism ◽  
Immune Receptor ◽  
Apoe Isoforms ◽  
Soluble Trem2 ◽  
Biophysical Study ◽  
The Brain

AbstractINTRODUCTIONTREM2 is an innate immune receptor expressed on myeloid cells including microglia in the brain. How TREM2 engages different ligands remains poorly understood.METHODSWe used comprehensive BLI analysis to investigate the TREM2 interactions with ApoE and monomeric amyloid beta (mAβ42).RESULTSTREM2 binding did not depend on ApoE lipidation, and there were only slight differences in affinity observed between ApoE isoforms (E4 > E3 > E2). Surprisingly, disease-linked TREM2 variants within a “basic patch” minimally impact ApoE binding. Instead, TREM2 has a unique hydrophobic surface that can bind to ApoE. This direct engagement requires the hinge region of ApoE. TREM2 directly binds mAβ42 and can potently inhibit Aβ42 polymerization, suggesting a potential mechanism for soluble TREM2 (sTREM2) in preventing AD pathogenesis.DISCUSSIONThese findings demonstrate that TREM2 has at least two separate surfaces to engage ligands and uncovers a potential function for sTREM2 in directly inhibiting Aβ polymerization.

scholarly journals Regulation of intracellular innate immune amyloid beta (aβ) clearance

2021 ◽  
Vol 17 (S5) ◽  
Author(s):  
Marianne Wettergreen ◽  
Berglind Gisladottir ◽  
Bjørn Eivind Kirsebom ◽  
Erik Christensen ◽  
Kulbhushan Sharma ◽  
...  
Keyword(s):  
Amyloid Beta ◽  
Innate Immune ◽  
Aβ Clearance

scholarly journals Synthetic amyloid beta does not induce a robust transcriptional response in innate immune cell culture systems

2021 ◽  
Author(s):  
Ivana Y Quiroga ◽  
Aimee E Cruikshank ◽  
Kathleen S M Reed ◽  
Marielle L Bond ◽  
Baggio A Evangelista ◽  
...  
Keyword(s):  
Amyloid Beta ◽  
Immune Cells ◽  
Immune Cell ◽  
Neuronal Damage ◽  
Transcriptional Response ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Cellular Models ◽  
A Genome

Alzheimer's disease (AD) is a progressive neurodegenerative disease that impacts nearly 400 million people worldwide. The accumulation of amyloid beta (Aβ) in the brain has historically been associated with AD, and recent evidence suggests that neuroinflammation plays a central role in its origin and progression. These observations have given rise to the theory that Aβ is the primary trigger of AD, and induces proinflammatory activation of immune brain cells (i.e. microglia), which culminates in neuronal damage and cognitive decline. In order to test this hypothesis, many in vitro systems have been established to study Aβ-mediated activation of innate immune cells. Nevertheless, the transcriptional resemblance of these models to the microglia in the AD brain has never been comprehensively studied on a genome-wide scale. To address this, we used bulk RNA-seq to assess the transcriptional differences between in vitro cell types used to model neuroinflammation in AD, including several established, primary and iPSC-derived immune cell lines (macrophages, microglia and astrocytes) and their similarities to primary cells in the AD brain. We then analyzed the transcriptional response of these innate immune cells to synthetic Aβ. We found that human induced pluripotent stem cell (hIPSC)-derived microglia (IMGL) are the in vitro cell model that best resembles primary microglia. Surprisingly, synthetic Aβ does not trigger a robust transcriptional response in any of the cellular models analyzed, despite testing a wide variety of Aβ formulations, concentrations, and treatment conditions. Finally, we found that bacterial LPS and INFγ activate microglia and induce transcriptional changes similar to those observed in disease associated microglia present in the AD brain, suggesting the potential suitability of this model to study AD-related neuroinflammation.

Proteolytic processing of the amyloid-beta protein precursor of Alzheimer's disease

2002 ◽  
Vol 38 ◽  
pp. 37-49 ◽  
Author(s):  
Janelle Nunan ◽  
David H Small
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Alternative Pathway ◽  
Protein A ◽  
Proteolytic Processing ◽  
Gamma Secretase ◽  
Amyloid Beta Protein ◽  
Protein Precursor ◽  
Amyloid Beta Protein Precursor

The proteolytic processing of the amyloid-beta protein precursor plays a key role in the development of Alzheimer's disease. Cleavage of the amyloid-beta protein precursor may occur via two pathways, both of which involve the action of proteases called secretases. One pathway, involving beta- and gamma-secretase, liberates amyloid-beta protein, a protein associated with the neurodegeneration seen in Alzheimer's disease. The alternative pathway, involving alpha-secretase, precludes amyloid-beta protein formation. In this review, we describe the progress that has been made in identifying the secretases and their potential as therapeutic targets in the treatment or prevention of Alzheimer's disease.

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