title: Autophagy in motor neuron disease: Key pathogenetic mechanisms and therapeutic targets.
abstract: Autophagy is a lysosome-dependant intracellular degradation process that eliminates long-lived proteins as well as damaged organelles from the cytoplasm. An increasing body of evidence suggests that dysregulation of this system plays a pivotal role in the etiology and/or progression of neurodegenerative diseases including motor neuron disorders. Herein, we review the latest findings that highlight the involvement of autophagy in the pathogenesis of amyotrophic lateral sclerosis (ALS) and the potential role of this pathway as a target of therapeutic purposes. Autophagy promotes the removal of toxic, cytoplasmic aggregate-prone pathogenetic proteins, enhances cell survival, and modulates inflammation. The existence of several drugs targeting this pathway can facilitate the translation of basic research to clinical trials for ALS and other motor neuron diseases.
authors.affiliation: Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, Istituto Di Ricovero e Cura a Carattere Scientifico Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy.
authors.forename: Maria Sara
authors.initials: MS
authors.lastname: Cipolat Mis
authors.affiliation: Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, Istituto Di Ricovero e Cura a Carattere Scientifico Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Brajkovic
authors.affiliation: Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, Istituto Di Ricovero e Cura a Carattere Scientifico Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Frattini
authors.affiliation: Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, Istituto Di Ricovero e Cura a Carattere Scientifico Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Di Fonzo
authors.affiliation: Dino Ferrari Center, Neuroscience Section, Department of Pathophysiology and Transplantation, University of Milan, Neurology Unit, Istituto Di Ricovero e Cura a Carattere Scientifico Foundation Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy. Electronic address: stefania.corti@unimi.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
mesh_terms: D000818:Animals; D001343:Autophagy; D055808:Drug Discovery; D006801:Humans; D058990:Molecular Targeted Therapy; D016472:Motor Neuron Disease / Q000188:drug therapy / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D058570:TOR Serine-Threonine Kinases
keywords: Amyotrophic lateral sclerosis; Authophagy; Protein aggregation