Conceived more than 25 years ago, the amyloid cascade hypothesis of Alzheimer's disease has evolved to accommodate new findings, namely different forms of β-amyloid aggregates and downstream dysfunctions. Yet, the cascade does not mention its very beginning, the β-amyloid monomer. Here, I will discuss the monomer from a functional evolutionary perspective, highlighting the potential advantages of a native unfolded state that, however, involves an amyloidogenic risk. Finally, I will make a summary of what is known about its functional role in the brain and discuss the implications of its conceivable shortage in the development of Alzheimer's disease.

The underexplored question of β-amyloid monomers

COPANI, Agata Graziella
2017-01-01

Abstract

Conceived more than 25 years ago, the amyloid cascade hypothesis of Alzheimer's disease has evolved to accommodate new findings, namely different forms of β-amyloid aggregates and downstream dysfunctions. Yet, the cascade does not mention its very beginning, the β-amyloid monomer. Here, I will discuss the monomer from a functional evolutionary perspective, highlighting the potential advantages of a native unfolded state that, however, involves an amyloidogenic risk. Finally, I will make a summary of what is known about its functional role in the brain and discuss the implications of its conceivable shortage in the development of Alzheimer's disease.
2017
Aβ monomer; Brain hypometabolism; Glut3; IGF-IR; Neuronal glucose uptake; Neuroprotection; Pharmacology
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/299123
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