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PMID: 8719038 Published · ppublish English Journal Article Review

Ion channel hypothesis for Alzheimer amyloid peptide neurotoxicity.

Cellular and molecular neurobiology ·Vol. 15 ·No. 5 ·1995-10-00 ·Pages 513-26

Pollard HB, Arispe N, Rojas E

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.

MeSH Terms
Alzheimer Disease/pathology,physiopathology Amino Acid Sequence Amyloid beta-Peptides/chemistry,physiology,toxicity Amyloid beta-Protein Precursor/chemistry,physiology Animals Brain/pathology,physiopathology Humans Ion Channels/chemistry,physiology Models, Neurological Models, Structural Molecular Sequence Data Neurotoxins Protein Structure, Secondary
Chemicals
Amyloid beta-Peptides Amyloid beta-Protein Precursor Ion Channels Neurotoxins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Pollard H B
Laboratory of Cell Biology and Genetics, NIDDSK, National Institutes of Health, Bethesda, MD 20892, USA.
Arispe N
Rojas E
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Article Info
Journal
Cellular and molecular neurobiology
Abbr.
Cell Mol Neurobiol
ISSN
0272-4340
DOI
10.1007/BF02071314
Published
1995-10-00
Pages
513-26
Language
English
Region
United States
NLM ID
8200709
Subset
IM
External Links
PubMed source DOI: 10.1007/BF02071314 View journal details
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