scholarly journals Recapitulation of spinal motor neuron-specific disease phenotypes in a human cell model of spinal muscular atrophy

Cell Research ◽  
2012 ◽  
Vol 23 (3) ◽  
pp. 378-393 ◽  
Author(s):  
Zhi-Bo Wang ◽  
Xiaoqing Zhang ◽  
Xue-Jun Li
Keyword(s):  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Human Cell ◽  
Muscular Atrophy ◽  
Cell Model ◽  
Spinal Motor Neuron ◽  
Disease Phenotypes ◽  
Specific Disease ◽  
Spinal Motor

scholarly journals Decreased microRNA levels lead to deleterious increases in neuronal M2 muscarinic receptors in Spinal Muscular Atrophy models

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Patrick J O'Hern ◽  
Inês do Carmo G. Gonçalves ◽  
Johanna Brecht ◽  
Eduardo Javier López Soto ◽  
Jonah Simon ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Spinal Motor Neuron ◽  
C Elegans ◽  
M2 Muscarinic Receptor ◽  
Smn Protein ◽  
Survival Of Motor Neuron ◽  
Microrna Function ◽  
M2 Muscarinic Receptors

Spinal Muscular Atrophy (SMA) is caused by diminished Survival of Motor Neuron (SMN) protein, leading to neuromuscular junction (NMJ) dysfunction and spinal motor neuron (MN) loss. Here, we report that reduced SMN function impacts the action of a pertinent microRNA and its mRNA target in MNs. Loss of the C. elegans SMN ortholog, SMN-1, causes NMJ defects. We found that increased levels of the C. elegans Gemin3 ortholog, MEL-46, ameliorates these defects. Increased MEL-46 levels also restored perturbed microRNA (miR-2) function in smn-1(lf) animals. We determined that miR-2 regulates expression of the C. elegans M2 muscarinic receptor (m2R) ortholog, GAR-2. GAR-2 loss ameliorated smn-1(lf) and mel-46(lf) synaptic defects. In an SMA mouse model, m2R levels were increased and pharmacological inhibition of m2R rescued MN process defects. Collectively, these results suggest decreased SMN leads to defective microRNA function via MEL-46 misregulation, followed by increased m2R expression, and neuronal dysfunction in SMA.

scholarly journals Inhibition of Apoptosis Blocks Human Motor Neuron Cell Death in a Stem Cell Model of Spinal Muscular Atrophy

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e39113 ◽  
Author(s):  
Dhruv Sareen ◽  
Allison D. Ebert ◽  
Brittany M. Heins ◽  
Jered V. McGivern ◽  
Loren Ornelas ◽  
...  
Keyword(s):  
Cell Death ◽  
Stem Cell ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Cell Model ◽  
Stem Cell Model ◽  
Human Motor
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