Synaptic dysfunction in Alzheimer's disease

Advances in Experimental Medicine and Biology
Elena MarcelloMonica Di Luca

Abstract

Generation of amyloid peptide (Aβ) is at the beginning of a cascade that leads to Alzheimer's disease (AD). Amyloid precursor protein (APP), as well as β- and γ-secretases, is the principal player involved in Aβ production, while α-secretase cleavage on APP prevents Aβ deposition. Recent studies suggested that soluble assembly states of Aβ peptides can cause cognitive problems by disrupting synaptic function in the absence of significant neurodegeneration. Therefore, current research investigates the relative importance of these various soluble Aβ assemblies in causing synaptic dysfunction and cognitive deficits. Several Aβ oligomers targets and cellular mechanisms responsible of Aβ-induced synaptic failure have been identified. The first and most important mechanism impugns a toxic gain of function for Aβ which results due to self-association and attainment of new structures capable of novel interactions that lead to impaired plasticity. Other scenarios predicate that Aβ has a normal physiological role. On the one hand, insufficient Aβ could lead to a loss of normal function, whereas excess Aβ may precipitate dysfunction. How this occurs and which the main target/s is/are for the synaptic action of Aβ remains to be fully under...Continue Reading

Citations

May 17, 2013·The Journal of Clinical Investigation·Elena MarcelloMonica Di Luca
Aug 27, 2013·PloS One·Bérangère DelegliseJean-Michel Peyrin
Jan 24, 2014·Molecular Neurobiology·Silvia BologninMario Buffelli
Oct 21, 2015·Communicative & Integrative Biology·Joern R Steinert
Feb 25, 2014·Communicative & Integrative Biology·Flaviano Giorgini, Joern R Steinert
Mar 24, 2017·Neuroscience Letters·Zhiwen YaoPeng Jia
Jun 20, 2017·European Journal of Pharmacology·Stefano Musardo, Elena Marcello
Jan 8, 2013·Neuropathology and Applied Neurobiology·T H Gillingwater, T M Wishart
Jan 3, 2014·Physiological Reviews·Carlo Sala, Menahem Segal
Jun 28, 2014·Molecular Medicine Reports·Shuifen YeJing Cai
Oct 12, 2019·The Journal of Cell Biology·Scott A TiscioneEamonn J Dickson
Jul 25, 2015·Journal of Neurochemistry·Elena MarcelloMonica Di Luca
Oct 15, 2019·Frontiers in Pharmacology·Emre FertanRichard E Brown
Sep 27, 2018·Frontiers in Cellular Neuroscience·Geoffrey CanetSara Salinas
May 4, 2017·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Walter E MüllerHans-Jürgen Möller
Apr 4, 2021·International Journal of Molecular Sciences·Susana López-OrtizAlejandro Santos-Lozano

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