title: Neuromuscular Junction Impairment in Amyotrophic Lateral Sclerosis: Reassessing the Role of Acetylcholinesterase.
abstract: Amyotrophic Lateral Sclerosis (ALS) is a highly debilitating disease caused by progressive degeneration of motorneurons (MNs). Due to the wide variety of genes and mutations identified in ALS, a highly varied etiology could ultimately converge to produce similar clinical symptoms. A major hypothesis in ALS research is the "distal axonopathy" with pathological changes occurring at the neuromuscular junction (NMJ), at very early stages of the disease, prior to MNs degeneration and onset of clinical symptoms. The NMJ is a highly specialized cholinergic synapse, allowing signaling between muscle and nerve necessary for skeletal muscle function. This nerve-muscle contact is characterized by the clustering of the collagen-tailed form of acetylcholinesterase (ColQ-AChE), together with other components of the extracellular matrix (ECM) and specific key molecules in the NMJ formation. Interestingly, in addition to their cholinergic role AChE is thought to play several "non-classical" roles that do not require catalytic function, most prominent among these is the facilitation of neurite growth, NMJ formation and survival. In all this context, abnormalities of AChE content have been found in plasma of ALS patients, in which AChE changes may reflect the neuromuscular disruption. We review these findings and particularly the evidences of changes of AChE at neuromuscular synapse in the pre-symptomatic stages of ALS.
authors.affiliation: Sorbonne Université, Université Pierre et Marie Curie (UPMC), Université de Paris 06, Unité Mixte 75, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 1127, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche 7225 Institut du Cerveau et de la Moelle Épinière (ICM) Paris, France.
authors.forename: Maria-Letizia
authors.initials: ML
authors.lastname: Campanari
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'AlacantSpain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)Madrid, Spain; Unidad de Investigación, Hospital General Universitario de Elche, FISABIOElche, Spain.
authors.forename: María-Salud
authors.initials: MS
authors.lastname: García-Ayllón
authors.affiliation: Sorbonne Université, Université Pierre et Marie Curie (UPMC), Université de Paris 06, Unité Mixte 75, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 1127, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche 7225 Institut du Cerveau et de la Moelle Épinière (ICM) Paris, France.
authors.forename: Sorana
authors.initials: S
authors.lastname: Ciura
authors.affiliation: Instituto de Neurociencias de Alicante, Universidad Miguel Hernández-CSIC, Sant Joan d'AlacantSpain; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Sáez-Valero
authors.affiliation: Sorbonne Université, Université Pierre et Marie Curie (UPMC), Université de Paris 06, Unité Mixte 75, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 1127, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche 7225 Institut du Cerveau et de la Moelle Épinière (ICM) Paris, France.
authors.forename: Edor
authors.initials: E
authors.lastname: Kabashi
keywords: acetylcholinesterase (AChE); amyotrophic lateral sclerosis (ALS); axonopathy; collagen tail subunit of asymmetric acetylcholinesterase (ColQ); neuromuscular junction (NMJ)