{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Simon CM"],"funding":["SMA Foundation","Cure SMA","NIAAA NIH HHS","NINDS NIH HHS","NIH"],"pagination":["3885-3901.e5"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6956708"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["29(12)"],"pubmed_abstract":["Reduced expression of the survival motor neuron (SMN) protein causes the neurodegenerative disease spinal muscular atrophy (SMA). Here, we show that adeno-associated virus serotype 9 (AAV9)-mediated delivery of Stasimon-a gene encoding an endoplasmic reticulum (ER)-resident transmembrane protein regulated by SMN-improves motor function in a mouse model of SMA through multiple mechanisms. In proprioceptive neurons, Stasimon overexpression prevents the loss of afferent synapses on motor neurons and enhances sensory-motor neurotransmission. In motor neurons, Stasimon suppresses neurodegeneration by reducing phosphorylation of the tumor suppressor p53. Moreover, Stasimon deficiency converges on SMA-related mechanisms of p53 upregulation to induce phosphorylation of p53 through activation of p38 mitogen-activated protein kinase (MAPK), and pharmacological inhibition of this kinase prevents motor neuron death in SMA mice. These findings identify Stasimon dysfunction induced by SMN deficiency as an upstream driver of distinct cellular cascades that lead to synaptic loss and motor neuron degeneration, revealing a dual contribution of Stasimon to motor circuit pathology in SMA."],"journal":["Cell reports"],"pubmed_title":["Stasimon Contributes to the Loss of Sensory Synapses and Motor Neuron Death in a Mouse Model of Spinal Muscular Atrophy."],"pmcid":["PMC6956708"],"funding_grant_id":["R01 NS102451","R21 NS098363","R21 NS077038","R01NS078375","R01 AA027079","R01AA027079","R21NS077038","R01NS102451","R01 NS078375","R21NS098363"],"pubmed_authors":["Lotti F","Mentis GZ","Van Alstyne M","Bianchetti E","Watterson DM","Pellizzoni L","Simon CM","Tisdale S"],"additional_accession":[]},"is_claimable":false,"name":"Stasimon Contributes to the Loss of Sensory Synapses and Motor Neuron Death in a Mouse Model of Spinal Muscular Atrophy.","description":"Reduced expression of the survival motor neuron (SMN) protein causes the neurodegenerative disease spinal muscular atrophy (SMA). Here, we show that adeno-associated virus serotype 9 (AAV9)-mediated delivery of Stasimon-a gene encoding an endoplasmic reticulum (ER)-resident transmembrane protein regulated by SMN-improves motor function in a mouse model of SMA through multiple mechanisms. In proprioceptive neurons, Stasimon overexpression prevents the loss of afferent synapses on motor neurons and enhances sensory-motor neurotransmission. In motor neurons, Stasimon suppresses neurodegeneration by reducing phosphorylation of the tumor suppressor p53. Moreover, Stasimon deficiency converges on SMA-related mechanisms of p53 upregulation to induce phosphorylation of p53 through activation of p38 mitogen-activated protein kinase (MAPK), and pharmacological inhibition of this kinase prevents motor neuron death in SMA mice. These findings identify Stasimon dysfunction induced by SMN deficiency as an upstream driver of distinct cellular cascades that lead to synaptic loss and motor neuron degeneration, revealing a dual contribution of Stasimon to motor circuit pathology in SMA.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Dec","modification":"2024-11-15T15:31:08.935Z","creation":"2020-05-22T07:55:18Z"},"accession":"S-EPMC6956708","cross_references":{"pubmed":["31851921"],"doi":["10.1016/j.celrep.2019.11.058"]}}