scholarly journals β-Amyloid Peptide Activates α7 Nicotinic Acetylcholine Receptors Expressed inXenopusOocytes

2002 ◽  
Vol 277 (28) ◽  
pp. 25056-25061 ◽  
Author(s):  
Kelly T. Dineley ◽  
Karen A. Bell ◽  
Duy Bui ◽  
J. David Sweatt
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Amyloid Peptide ◽  
Nicotinic Acetylcholine ◽  
Α7 Nicotinic Acetylcholine Receptors ◽  
Β Amyloid ◽  
Β Amyloid Peptide

β-Amyloid Peptide Activates Non-α7 Nicotinic Acetylcholine Receptors in Rat Basal Forebrain Neurons

2003 ◽  
Vol 90 (5) ◽  
pp. 3130-3136 ◽  
Author(s):  
Wen Fu ◽  
Jack H. Jhamandas
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Basal Forebrain ◽  
Single Channel ◽  
Amyloid Peptide ◽  
Nicotinic Acetylcholine ◽  
Whole Cell ◽  
Β Amyloid ◽  
Forebrain Neurons ◽  
Β Amyloid Peptide ◽  
Α7 Nachrs

Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by profound deficits in memory and cognitive function. Neuropathological hallmarks of the disease include a loss of basal forebrain cholinergic neurons and the deposition of β-amyloid peptide (Aβ) in neuritic plaques. At a cellular level, considerable attention has focused on a study of Aβ interactions with the neuronal nicotinic acetylcholine receptor (nAChR) subtypes. In this study, using cell-attached and outside-out single channel recordings from acutely dissociated rat basal forebrain neurons, we report that Aβ and nicotine activate nAChRs with two distinct levels of single-channel conductance. Whole cell recordings from these neurons reveal Aβ and nicotine, in a concentration-dependent and reversible manner, evoke brisk depolarizing responses and an inward current. The effects of Aβ on both single channel and whole cell are blocked by the noncompetitive nAChR antagonist mecamylamine and competitive nAChR antagonist dihydro-beta-erythroidine, but not the specific α7-selective nAChR antagonist methyllycaconitine, indicating that Aβ activated non-α7 nAChRs on basal forebrain neurons. In addition, the non-α7 nAChR agonists UB-165, epibatidine, and cytisine, but not the selective α7 agonist AR-R17779, induced similar responses as Aβ and nicotine. Thus non-α7 nAChRs may also represent a novel target in mediating the effects of Aβ in AD.

scholarly journals Choline Modulation of the Aβ P1-40 Channel Reconstituted into a Model Lipid Membrane

2010 ◽  
Vol 2010 ◽  
pp. 1-12
Author(s):  
Daniela Meleleo ◽  
Gabriella Notarachille ◽  
Silvia Micelli
Keyword(s):  
Lipid Bilayers ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Lipid Membrane ◽  
Cd Spectroscopy ◽  
Amyloid Peptide ◽  
Random Coil ◽  
Ion Conductance ◽  
Β Amyloid ◽  
Β Amyloid Peptide

Nicotinic acetylcholine receptors (AChRs), implicated in memory and learning, in subjects affected by Alzheimer's disease result altered. Stimulation of α7-nAChRs inhibits amyloid plaques and increases ACh release. β-amyloid peptide (AβP) forms ion channels in the cell and model phospholipid membranes that are retained responsible in Alzheimer disease. We tested if choline, precursor of ACh, could affect the AβP1-40 channels in oxidized cholesterol (OxCh) and in palmitoyl-oleoyl-phosphatidylcholine (POPC):Ch lipid bilayers. Choline concentrations of 5 × 10−11 M–1.5 × 10−8 M added to thecis- ortrans-side of membrane quickly increased AβP1-40 ion channel frequency (events/min) and ion conductance in OxCh membranes, but not in POPC:Ch membranes. Circular Dichroism (CD) spectroscopy shows that after 24 and 48 hours of incubation with AβP1-40, choline stabilizes the random coil conformation of the peptide, making it less prone to fibrillate. These actions seem to be specific in that ACh is ineffective either in solution or on AβP1-40 channel incorporated into PLMs.

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