Beta-amyloid short- and long-term synaptic entanglement

Publication date: Available online 22 November 2018Source: Pharmacological ResearchAuthor(s): Cristina Lanni, Francesca Fagiani, Marco Racchi, Stefania Preda, Alessia Pascale, Massimo Grilli, Nicola Allegri, Stefano GovoniAbstractBeta-amyloid (Aβ) is a peptide that derives from the proteolytic cleavage of the amyloid precursor protein (APP) by several secretases. Since its isolation and sequencing from Alzheimer’s disease (AD) brains, Aβ has been intensively investigated in the context of AD as the main pathogenic marker responsible for neurodegenerative processes. During the last three decades, results from several independent studies have converged to form the so-called amyloid cascade hypothesis of AD and several therapeutic strategies designed to modulate the APP amyloidogenic pathway have been developed. However, none of the clinical trials targeting Aβ culminated in a significant clinical outcome, thus challenging the concept that targeting Aβ, at least within the time window so far explored in clinical trials, may have a therapeutic effect. However, besides its presence in AD brains, brain cells produce Aβ, thus suggesting that, under normal conditions, the peptide may have a role in the regulation of brain functions, which is consistent with its ubiquitous presence and normal synthesis. Taking into account that Aβ has been found to exhibit a dual role strictly correlated with its concentration (neuromodulatory/neuroprotective vs neurotoxic), we discuss emergin...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research