scholarly journals Stasimon Contributes to the Loss of Sensory Synapses and Motor Neuron Death in a Mouse Model of Spinal Muscular Atrophy

2019 ◽  
Author(s):  
Christian Simon ◽  
Meaghan Van Alstyne ◽  
Francesco Lotti ◽  
Elena Bianchetti ◽  
Sarah Tisdale ◽  
...  
Keyword(s):  
Mouse Model ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Neuron Death ◽  
Motor Neuron Death

scholarly journals Stasimon Contributes to the Loss of Sensory Synapses and Motor Neuron Death in a Mouse Model of Spinal Muscular Atrophy

Cell Reports ◽  
2019 ◽  
Vol 29 (12) ◽  
pp. 3885-3901.e5 ◽  
Author(s):  
Christian M. Simon ◽  
Meaghan Van Alstyne ◽  
Francesco Lotti ◽  
Elena Bianchetti ◽  
Sarah Tisdale ◽  
...  
Keyword(s):  
Mouse Model ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Neuron Death ◽  
Motor Neuron Death

Possible pathogenic role of muscle cell dysfunction in motor neuron death in spinal muscular atrophy

2002 ◽  
Vol 25 (5) ◽  
pp. 700-708 ◽  
Author(s):  
S�verine Guettier-Sigrist ◽  
B�n�dicte Hugel ◽  
Gilliane Coupin ◽  
Jean-Marie Freyssinet ◽  
Philippe Poindron ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscle Cell ◽  
Muscular Atrophy ◽  
Pathogenic Role ◽  
Neuron Death ◽  
Cell Dysfunction ◽  
Motor Neuron Death

scholarly journals Dysregulation of Mdm2 and Mdm4 alternative splicing underlies motor neuron death in spinal muscular atrophy

2018 ◽  
Vol 32 (15-16) ◽  
pp. 1045-1059 ◽  
Author(s):  
Meaghan Van Alstyne ◽  
Christian M. Simon ◽  
S. Pablo Sardi ◽  
Lamya S. Shihabuddin ◽  
George Z. Mentis ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Neuron Death ◽  
Motor Neuron Death

scholarly journals Stasimon contributes to the loss of sensory synapses and motor neuron death in a mouse model of spinal muscular atrophy

2019 ◽  
Author(s):  
Christian M. Simon ◽  
Meaghan Van Alstyne ◽  
Francesco Lotti ◽  
Elena Bianchetti ◽  
Sarah Tisdale ◽  
...  
Keyword(s):  
Mouse Model ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Muscular Atrophy ◽  
Transmembrane Protein ◽  
Neuron Death ◽  
Gene Encoding ◽  
Neurodegenerative Process ◽  
Smn Protein

AbstractReduced expression of the SMN protein causes spinal muscular atrophy (SMA) – an inherited neurodegenerative disease characterized by multiple synaptic deficits and motor neuron loss. Here, we show that AAV9-mediated delivery of Stasimon – a gene encoding an ER-resident transmembrane protein regulated by SMN – improves motor function in a mouse model of SMA through multiple mechanisms. In proprioceptive neurons of SMA mice, Stasimon overexpression prevents the loss of afferent synapses on motor neurons and enhances sensory-motor neurotransmission. In SMA motor neurons, Stasimon suppresses the neurodegenerative process by selectively reducing phosphorylation but not upregulation of the tumor suppressor p53, both of which are converging events required to trigger neuronal death. We further show that Stasimon deficiency synergizes with SMA-related mechanisms of p53 upregulation to induce phosphorylation of p53. These findings identify Stasimon dysfunction induced by SMN deficiency as an upstream driver of cellular pathways that lead to synaptic loss and motor neuron degeneration, revealing a dual contribution of Stasimon to motor circuit pathology in SMA.

scholarly journals Teaching an old drug new tricks: repositioning strategies for spinal muscular atrophy

2019 ◽  
Vol 14 (3) ◽  
pp. FNL25
Author(s):  
Joseph M Hoolachan ◽  
Emma R Sutton ◽  
Melissa Bowerman
Keyword(s):  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Genetic Therapy ◽  
Neuron Death ◽  
Muscle Disorders ◽  
Motor Neuron Death ◽  
Smn Gene ◽  
New Treatments ◽  
Spinal Cord Motor Neuron ◽  
Maximal Benefit

Spinal muscular atrophy (SMA) is a childhood disorder caused by loss of the SMN gene. Pathological hallmarks are spinal cord motor neuron death, neuromuscular junction dysfunction and muscle atrophy. The first SMN genetic therapy was recently approved and other SMN-dependent treatments are not far behind. However, not all SMA patients will reap their maximal benefit due to limited accessibility, high costs and differential effects depending on timing of administration and disease severity. The repurposing of commercially available drugs is an interesting strategy to ensure more rapid and less expensive access to new treatments. In this mini-review, we will discuss the potential and relevance of repositioning drugs currently used for neurodegenerative, neuromuscular and muscle disorders for SMA.

scholarly journals Pre-symptomatic development of lower motor neuron connectivity in a mouse model of severe spinal muscular atrophy

2009 ◽  
Vol 19 (3) ◽  
pp. 420-433 ◽  
Author(s):  
Lyndsay M. Murray ◽  
Sheena Lee ◽  
Dirk Bäumer ◽  
Simon H. Parson ◽  
Kevin Talbot ◽  
...  
Keyword(s):  
Mouse Model ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Lower Motor Neuron

scholarly journals Calpain-Dependent Degradation of Nucleoporins Contributes to Motor Neuron Death in a Mouse Model of Chronic Excitotoxicity

2017 ◽  
Vol 37 (36) ◽  
pp. 8830-8844 ◽  
Author(s):  
Kaori Sugiyama ◽  
Tomomi Aida ◽  
Masatoshi Nomura ◽  
Ryoichi Takayanagi ◽  
Hanns U. Zeilhofer ◽  
...  
Keyword(s):  
Mouse Model ◽  
Motor Neuron ◽  
Neuron Death ◽  
Motor Neuron Death

scholarly journals The primary locus of motor neuron death in an ALS–PDC mouse model

Neuroreport ◽  
2009 ◽  
Vol 20 (14) ◽  
pp. 1284-1289 ◽  
Author(s):  
Grace Lee ◽  
Tony Chu ◽  
Christopher A. Shaw
Keyword(s):  
Mouse Model ◽  
Motor Neuron ◽  
Neuron Death ◽  
Motor Neuron Death
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