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Hormetic effect of amyloid-beta peptide in synaptic plasticity and memory.
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.
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Picomolar concentrations of Aβ are sufficient to stimulate nicotinic receptors and subsequently LTP and learning and memory in healthy rodents.
“picomolar concentrations of Aβ are sufficient to stimulate nicotinic receptors and subsequently LTP and learning and memory in healthy rodents (Puzzo et al., 2008, 2012; Morley et al., 2010)”
From Emerging Alternative Proteinases in APP Metabolism and Alzheimer’s Disease Pathogenesis: A Focus on MT1-MMP and MT5-MMP (2019) · cites this paper as Puzzo et al., 2012
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Picomolar Amyloid-β Positively Modulates Synaptic Plasticity and Memory in Hippocampus
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Metadata
- Authors
- Puzzo, D., Privitera, L., & Palmeri, A.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 33
- Issue
- 7
- Pages
- 1484.e15-1484.e24
- ISSN
- 0197-4580
- Cited by
- 95
- References
- 7
- Language
- en
- Funders
- Alzheimer's Association (IIRG-09-134220)
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