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Soluble Aβ oligomer-induced synaptopathy: c-Jun N-terminal kinase's role Free
Alessandra Sclip1, Andrea Arnaboldi1, Isabella Colombo1, Pietro Veglianese1, Laura Colombo1, Massimo Messa1, Simona Mancini1, Sara Cimini1, Federica Morelli1, Xanthi Antoniou1, Egbert Welker2, Mario Salmona1, and Tiziana Borsello1,*
1IRCCS-Istituto di Ricerche Farmacologiche ‘Mario Negri’, Via La Masa 19, 20156 Milano, Italy
2Département de Neurosciences Fondamentales, University of Lausanne, 1005 Lausanne, Switzerland
*Correspondence to:Tiziana Borsello, E-mail: tiziana.borsello@marionegri.it
J Mol Cell Biol, Volume 5, Issue 4, August 2013, 277-279,  https://doi.org/10.1093/jmcb/mjt015

Among the neurodegenerative diseases, Alzheimer disease (AD) is the most common and severe age-related dementia for which there is currently no available treatment. Many studies support the assumption that AD is a spine pathology (Selkoe, 2002; Sivanesan et al., 2013) and that soluble amyloid-β (Aβ) oligomers are causative of AD synaptopathy. Diverse lines of evidence indicate that Aβ oligomers induce formation of pore-like structures on the membrane (Arispe et al., 1993; Lashuel et al., 2002) and interfere with glutamatergic transmission. The Aβ oligomers result in a decreased number of AMPA receptors (AMPA-r) and NMDA receptors (NMDA-r), as well as PSD-95 at the postsynaptic membrane, and thus reduce the strength and plasticity of excitatory synapses (Chapman et al., 1999; Walsh et al., 2002). However, the underlying intracellular mechanisms regulating synaptic changes are only partially known. By understanding the pathophysiological mechanisms leading to synaptic dysfunction and the progression of this dysfunction, better interference in the pathogenesis of AD can be achieved.