Alzheimer's disease: inside, outside, upside down

2001 ◽  
Vol 67 ◽  
pp. 15-22 ◽  
Author(s):  
Shi Du Yan ◽  
Ann M. Schmidt ◽  
David Stern
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Surface ◽  
Advanced Glycation Endproducts ◽  
Amyloid Peptide ◽  
Cell Surface Receptor ◽  
Intracellular Enzyme ◽  
Cellular Targets ◽  
Surface Receptor ◽  
High Concentrations

Neurotoxicity of ϐ-amyloid peptide (Aϐ) in Alzheimer's disease (AD) is usually thought to arise from the nonspecific effects of high concentrations of Aϐ on vulnerable neurons, resulting in membrane destabilization and increasing intracellular calcium concentration. This review advances the hypothesis that at early stages of AD, when Aϐ is present in lower amounts, its ability to perturb the function of cellular targets is mediated by specific cofactors present on the cell surface and intracellularly. Receptor for advanced glycation endproducts (RAGE) is a cell-surface receptor which binds Aϐ and amplifies its effects on cells in the nanomolar range. The intracellular enzyme Aϐ-binding alcohol dehydrogenase (ABAD) is likely to engage nascent Aϐ formed in the endoplasmic reticulum, and to mediate cell stress from this site. The analysis of Aϐ interaction with RAGE and ABAD, as well as other cofactors, provides insight into new mechanisms and, potentially, identifies therapeutic targets relevant to neuronal dysfunction in AD.

The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor

Nature ◽  
1987 ◽  
Vol 325 (6106) ◽  
pp. 733-736 ◽  
Author(s):  
Jie Kang ◽  
Hans-Georg Lemaire ◽  
Axel Unterbeck ◽  
J. Michael Salbaum ◽  
Colin L. Masters ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Surface ◽  
Cell Surface Receptor ◽  
Surface Receptor ◽  
A Cell

scholarly journals Effects of S100B on Serotonergic Plasticity and Neuroinflammation in the Hippocampus in Down Syndrome and Alzheimer's Disease: Studies in an S100B Overexpressing Mouse Model

2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Lee A. Shapiro ◽  
Lynn A. Bialowas-McGoey ◽  
Patricia M. Whitaker-Azmitia
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Down Syndrome ◽  
Transgenic Animals ◽  
Significant Loss ◽  
Cell Surface Receptor ◽  
Mammalian Brain ◽  
Surface Receptor ◽  
Glial Changes

S100B promotes development and maturation in the mammalian brain. However, prolonged or extensive exposure can lead to neurodegeneration. Two important functions of S100B in this regard, are its role in the development and plasticity of the serotonergic neurotransmitter system, and its role in the cascade of glial changes associated with neuroinflammation. Both of these processes are therefore accelerated towards degeneration in disease processes wherein S100B is increased, notably, Alzheimer's disease (AD) and Down syndrome (DS). In order to study the role of S100B in this context, we have examined S100B overexpressing transgenic mice. Similar to AD and DS, the transgenic animals show a profound change in serotonin innervation. By 28 weeks of age, there is a significant loss of terminals in the hippocampus. Similarly, the transgenic animals show neuroinflammatory changes analogous with AD and DS. These include decreased numbers of mature, stable astroglial cells, increased numbers of activated microglial cells and increased microglial expression of the cell surface receptor RAGE. Eventually, the S100B transgenic animals show neurodegeneration and the appearance of hyperphosphorylated tau structures, as seen in late stage DS and AD. The role of S100B in these conditions is discussed.

THE TRIGGERING RECEPTOR EXPRESSED ON MYELOID CELLS-2 (TREM-2) AS EXPRESSION OF THE RELATIONSHIP BETWEEN MICROGLIA AND ALZHEIMER’S DISEASE: A NOVEL MARKER FOR A PROMISING PATHWAY TO EXPLORE

2018 ◽  
pp. 1-3
Author(s):  
C. Gussago ◽  
M. Casati ◽  
E. Ferri ◽  
B. Arosio
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Variants ◽  
Neurodegenerative Disorder ◽  
Myeloid Cells ◽  
Cell Surface Receptor ◽  
Surface Receptor ◽  
A Cell ◽  
The Relationship ◽  
Common Neurodegenerative Disorder

Alzheimer’s disease (AD) is a common neurodegenerative disorder, strongly related with age. It has been reported that genetic variants of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2), a cell-surface receptor expressed in microglial cells, greatly increase the risk of AD, thus suggesting an involvement of the microglia in the AD pathogenesis. The aim of this report is to provide an overview of the TREM2 and of its possible implication in the pathogenesis of AD.

Expression, function, and localization of the REG cell surface receptor

2001 ◽  
Vol 120 (5) ◽  
pp. A18-A19
Author(s):  
B DIECKGRAEFE ◽  
C HOUCHEN ◽  
H ZHANG
Keyword(s):  
Cell Surface ◽  
Cell Surface Receptor ◽  
Surface Receptor

Inhibition of rat ventricular automaticity by adenosine

1985 ◽  
Vol 248 (6) ◽  
pp. H907-H913 ◽  
Author(s):  
L. J. Heller ◽  
R. A. Olsson
Keyword(s):  
Cell Surface ◽  
Cell Surface Receptor ◽  
Chronotropic Effect ◽  
Surface Receptors ◽  
Adenosine Concentration ◽  
Surface Receptor ◽  
Ventricular Automaticity ◽  
Beating Rate ◽  
Chronotropic Effects ◽  
Developed Pressure

This study was designed to characterize adenosine's negative chronotropic effect on ventricular pacemakers. The spontaneous beating rate of isolated, isovolumic rat ventricular preparations perfused with Krebs-Henseleit solution decreased as the adenosine concentration was increased [log M effective concentration 50% (EC50) = -5.22 +/- 0.17]. The lack of effect of propranolol or atropine on this adenosine response eliminates the involvement of endogenous neurotransmitters. Support for the involvement of an external cell surface receptor was provided by findings that theophylline and 8-(4-sulfophenyl)theophylline, an analogue thought to act solely at the cell surface, significantly increased the adenosine log M EC50 to -3.94 +/- 0.22 and -3.61 +/- 0.22, respectively. An increase in spontaneous beating rate induced by theophylline, but not by its analogue, was blocked by the addition of propranolol. The relative chronotropic potency of the adenosine analogues R-PIA, S-PIA, and NECA suggests that the cell surface receptors may be of the Ri type. The negative chronotropic effects of adenosine and its analogues occurred at concentrations that had no effect on the developed pressure of the paced preparation. Electrocardiographic evaluations indicate that at high agonist concentrations, there was an abrupt alteration in electrical properties of the preparation, which could be blocked by theophylline and its analogue.

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