title: Is spinal muscular atrophy a disease of the motor neurons only: pathogenesis and therapeutic implications?
abstract: Spinal muscular atrophy (SMA) is a genetic neurological disease that causes infant mortality; no effective therapies are currently available. SMA is due to homozygous mutations and/or deletions in the survival motor neuron 1 gene and subsequent reduction of the SMN protein, leading to the death of motor neurons. However, there is increasing evidence that in addition to motor neurons, other cell types are contributing to SMA pathology. In this review, we will discuss the involvement of non-motor neuronal cells, located both inside and outside the central nervous system, in disease onset and progression. Even if SMN restoration in motor neurons is needed, it has been shown that optimal phenotypic amelioration in animal models of SMA requires a more widespread SMN correction. It has been demonstrated that non-motor neuronal cells are also involved in disease pathogenesis and could have important therapeutic implications. For these reasons it will be crucial to take this evidence into account for the clinical translation of the novel therapeutic approaches.
authors.affiliation: Neuroscience Section, Neurology Unit, Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, University of Milan, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Simone
authors.affiliation: Neuroscience Section, Neurology Unit, Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, University of Milan, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Ramirez
authors.affiliation: Neuroscience Section, Neurology Unit, Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, University of Milan, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Bucchia
authors.affiliation: Neuroscience Section, Neurology Unit, Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, University of Milan, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Rinchetti
authors.affiliation: Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens (BRFAA), Soranou Efesiou 4, 115 27, Athens, Greece.
authors.forename: Hardy
authors.initials: H
authors.lastname: Rideout
authors.affiliation: Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens (BRFAA), Soranou Efesiou 4, 115 27, Athens, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Papadimitriou
authors.affiliation: Department of Environmental Health Sciences, Columbia University, New York, NY, 10032, USA.|Center for Motor Neuron Biology and Disease, Columbia University, New York, NY, 10032, USA.
authors.forename: Diane B
authors.initials: DB
authors.lastname: Re
authors.affiliation: Neuroscience Section, Neurology Unit, Department of Pathophysiology and Transplantation (DEPT), Dino Ferrari Centre, University of Milan, IRCCS Foundation Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122, Milan, Italy. stefania.corti@unimi.it.
authors.forename: Stefania
authors.initials: S
authors.lastname: Corti
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000473:pathology; D006801:Humans; D007107:Immune System / Q000473:pathology; D008099:Liver / Q000473:pathology; D009046:Motor Neurons / Q000473:pathology; D032342:Muscle Cells / Q000473:pathology*; D009134:Muscular Atrophy, Spinal / Q000150:complications / Q000473:pathology* / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D009457:Neuroglia / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D010179:Pancreas / Q000473:pathology; D012583:Schwann Cells / Q000473:pathology*
keywords: Central nervous system; Pathogenesis; Spinal muscular atrophy; Therapy