The Aβ peptides causally associated with Alzheimer disease have been seen as seemingly purposeless species produced by intramembrane cleavage under both physiological and pathological conditions. However, it has been increasingly suggested that they could instead constitute an ancient, highly conserved effector component of our innate immune system, dedicated to protecting the brain against microbial attacks. In this antimicrobial protection hypothesis, Aβ aggregation would switch from an abnormal stochastic event to a dysregulated innate immune response. In this perspective, we approach the problem from a different and complementary perspective by comparing the structure and sequence of Aβ(1-42) with those of bona fide antimicrobial peptides. We demonstrate that Aβ(1-42) bears convincing structural similarities with both viral fusion domains and antimicrobial peptides, as well as sequence similarities with a specific family of bacterial bacteriocins. We suggest a model of the mechanism by which Aβ peptides could elicit the immune response against microbes.

Why does the Aβ peptide of Alzheimer share structural similarity with antimicrobial peptides?

Raimondi F.;
2020

Abstract

The Aβ peptides causally associated with Alzheimer disease have been seen as seemingly purposeless species produced by intramembrane cleavage under both physiological and pathological conditions. However, it has been increasingly suggested that they could instead constitute an ancient, highly conserved effector component of our innate immune system, dedicated to protecting the brain against microbial attacks. In this antimicrobial protection hypothesis, Aβ aggregation would switch from an abnormal stochastic event to a dysregulated innate immune response. In this perspective, we approach the problem from a different and complementary perspective by comparing the structure and sequence of Aβ(1-42) with those of bona fide antimicrobial peptides. We demonstrate that Aβ(1-42) bears convincing structural similarities with both viral fusion domains and antimicrobial peptides, as well as sequence similarities with a specific family of bacterial bacteriocins. We suggest a model of the mechanism by which Aβ peptides could elicit the immune response against microbes.
2020
Settore BIO/11 - Biologia Molecolare
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11384/94324
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