One of the hot topics in Alzheimer's disease research field is the "amyloid hypothesis" postulating that the increase and deposition of beta-amyloid peptides (Aβ) is the main pathogenetic factor. However, antiamyloid-based therapies have so far been a failure and, most importantly, growing evidences suggest that Aβ has important physiologic functions. Based on our previous findings demonstrating that low concentrations of Aβ enhanced both synaptic plasticity and memory, whereas high concentrations induced the well-known impairment of cognition, here we show that Aβ acts on hippocampal long-term potentiation and reference memory drawing biphasic dose-response curves. This phenomenon, characterized by low-dose stimulation and high-dose inhibition and represented by a U-shaped or inverted-U-shaped curve, resembles the characteristics of hormesis. The Aβ double role raises important issues on the use of Aβ level reducing agents in Alzheimer's disease.

Hormetic effect of amyloid-beta peptide in synaptic plasticity and memory

PUZZO, DANIELA;PALMERI, Agostino
2012

Abstract

One of the hot topics in Alzheimer's disease research field is the "amyloid hypothesis" postulating that the increase and deposition of beta-amyloid peptides (Aβ) is the main pathogenetic factor. However, antiamyloid-based therapies have so far been a failure and, most importantly, growing evidences suggest that Aβ has important physiologic functions. Based on our previous findings demonstrating that low concentrations of Aβ enhanced both synaptic plasticity and memory, whereas high concentrations induced the well-known impairment of cognition, here we show that Aβ acts on hippocampal long-term potentiation and reference memory drawing biphasic dose-response curves. This phenomenon, characterized by low-dose stimulation and high-dose inhibition and represented by a U-shaped or inverted-U-shaped curve, resembles the characteristics of hormesis. The Aβ double role raises important issues on the use of Aβ level reducing agents in Alzheimer's disease.
hormesis; amyloid-beta; memory
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/11652
Citazioni
  • ???jsp.display-item.citation.pmc??? 42
  • Scopus 87
  • ???jsp.display-item.citation.isi??? 86
social impact