Beta-Amyloid oligomeric and monomeric states: implications for Alzheimer's Disease
type: CreativeWork
description: Alzheimer's Disease (AD) is by far the most common cause of dementia affecting more than 35 million people worldwide. Despite considerable research, there is still no cure for this neurodegenerative disease and available treatments are only symptomatic. In the controversial literature about AD, a predominant idea refers to the crucial role of amyloid-beta protein (Abeta) in the pathogenesis of the disease; in fact, the feature in the brain of AD patients is the presence of extracellular plaques mainly composed of Abeta. Nevertheless, Abeta is physiologically produced in healthy individuals. Due to its biophysical properties, under certain conditions, Abeta may self-aggregate into multiple forms, ranging from 4 kDa monomers and including higher-order oligomers, protofibrils, and mature fibrils. For many years, the fibrillar Abeta assemblies, similar to what seen in amyloid plaques, have been considered mainly responsible for neurodegenation associated with AD. However, the quantity and temporal progression of amyloid plaques do not correlate well with the clinical evolution of the disease. There is now extensive evidence that soluble Abeta oligomers disrupt synaptic transmission and plasticity in AD. Moreover, new studies strengthen evidence that people with sporadic AD make normal amounts of Abeta, and that the toxic buildup is due to altered peptide disposal. These data are in line with the finding previously reported by our group that Abeta in its non-toxic monomeric state has a broad neuroprotective effect in vitro. This effect depends on the stimulation of type-1 insulin-like growth factor (IGF-I) receptors and/or other receptors of the insulin superfamily. The aim of this PhD thesis was to decipher Abeta activities, focusing on the relationship between the structure/aggregation state and the neurotoxic/biological activity. In paper I we have addressed the issue of Abeta toxicity, whereas the properties of the non-toxic form of Abeta, the monomer, have been cons…
abstract: Alzheimer's Disease (AD) is by far the most common cause of dementia affecting more than 35 million people worldwide. Despite considerable research, there is still no cure for this neurodegenerative disease and available treatments are only symptomatic. In the controversial literature about AD, a predominant idea refers to the crucial role of amyloid-beta protein (Abeta) in the pathogenesis of the disease; in fact, the feature in the brain of AD patients is the presence of extracellular plaques mainly composed of Abeta. Nevertheless, Abeta is physiologically produced in healthy individuals. Due to its biophysical properties, under certain conditions, Abeta may self-aggregate into multiple forms, ranging from 4 kDa monomers and including higher-order oligomers, protofibrils, and mature fibrils. For many years, the fibrillar Abeta assemblies, similar to what seen in amyloid plaques, have been considered mainly responsible for neurodegenation associated with AD. However, the quantity and temporal progression of amyloid plaques do not correlate well with the clinical evolution of the disease. There is now extensive evidence that soluble Abeta oligomers disrupt synaptic transmission and plasticity in AD. Moreover, new studies strengthen evidence that people with sporadic AD make normal amounts of Abeta, and that the toxic buildup is due to altered peptide disposal. These data are in line with the finding previously reported by our group that Abeta in its non-toxic monomeric state has a broad neuroprotective effect in vitro. This effect depends on the stimulation of type-1 insulin-like growth factor (IGF-I) receptors and/or other receptors of the insulin superfamily. The aim of this PhD thesis was to decipher Abeta activities, focusing on the relationship between the structure/aggregation state and the neurotoxic/biological activity. In paper I we have addressed the issue of Abeta toxicity, whereas the properties of the non-toxic form of Abeta, the monomer, have been cons…
author: TOMASELLO, MARIANNA
language: eng
keywords: Beta-amyloid, insulin, insulin-like growth factor 1, Alzheimer's disease, neuronal death,glucose metabolism
date published: 2012-12-06
date modified: 2026-07-24T01:34:49Z
provider: Università degli Studi di Catania
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli studi di Catania

PropertyValue
property ID: Handle
value: https://hdl.handle.net/20.500.11769/586548