Ion Channel Hypothesis for Alzheimer Amyloid Peptide Neurotoxicity

Overview

Journal Cell Mol Neurobiol

Publisher Springer

Specialties Cell Biology
Molecular Biology
Neurology

Date 1995 Oct 1

PMID 8719038

Citations 26

Authors

H B Pollard

N Arispe

E Rojas

Affiliations

Soon will be listed here.

Abstract

1. Alzheimer's disease (AD) is a chronic dementia and neurodegenerative disorder affecting the oldest portions of the population. Brains of AD patients accumulate large amount of the A beta P peptide in amyloid plaques. 2. The A beta P[1-40] peptide is derived by proteolytic processing from a much larger amyloid precursor protein (APP), and has been circumstantially identified as the toxic principle causing cell damage in the disease. 4. The A beta P[1-40] peptide is able to form quite characteristic calcium channels in planar lipid bilayers. These channels have conductances in the nS range, and can dissipate ion gradients quickly. The peptide can also cause equivalent cation conductances in cells. 5. We suggest that amyloid channel blocking agents might be therapeutically useful in Alzheimer's Disease, and have constructed molecular models of the channels to aid in the design of such compounds.

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