Genomes and Genes
survival of motor neuron 1 protein
Summary: An SMN complex protein that contains a TUDOR DOMAIN and is essential for the function of the SMN protein complex. In humans, the protein is encoded by a single gene found near the inversion TELOMERE of a large inverted region of CHROMOSOME 5. Mutations in the gene coding for survival of motor neuron 1 protein may result in SPINAL MUSCULAR ATROPHIES OF CHILDHOOD.
- Martin J, Nguyen T, Grunseich C, Nofziger J, Lee P, Fields D, et al. Decreased Motor Neuron Support by SMA Astrocytes due to Diminished MCP1 Secretion. J Neurosci. 2017;37:5309-5318 pubmed publisher..This study reveals a novel aspect of astrocyte dysfunction in SMA and indicates a possible approach for improving motor neuron growth and survival in this disease. ..
- Mendell J, Al Zaidy S, Shell R, Arnold W, Rodino Klapac L, Prior T, et al. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. N Engl J Med. 2017;377:1713-1722 pubmed publisher..Further studies are necessary to confirm the safety and efficacy of this gene therapy. (Funded by AveXis and others; ClinicalTrials.gov number, NCT02122952 .). ..
- Paton D. Nusinersen: antisense oligonucleotide to increase SMN protein production in spinal muscular atrophy. Drugs Today (Barc). 2017;53:327-337 pubmed publisher..In addition, there have been significant extensions in life expectancy. These findings led to the U.S. and European approval of nusinersen for use in SMA patients of all ages. ..
- Li W. How do SMA-linked mutations of SMN1 lead to structural/functional deficiency of the SMA protein?. PLoS ONE. 2017;12:e0178519 pubmed publisher..From the computational analysis, it is also possible that SMN's Lys45 and Asp36 act as two electrostatic clips at the SMN-Gemin2 complex structure interface. ..
- Rietz A, Li H, Quist K, Cherry J, Lorson C, Burnett B, et al. Discovery of a Small Molecule Probe That Post-Translationally Stabilizes the Survival Motor Neuron Protein for the Treatment of Spinal Muscular Atrophy. J Med Chem. 2017;60:4594-4610 pubmed publisher..This series post-translationally stabilizes the SMN protein, unrelated to global proteasome or autophagy inhibition, revealing a novel therapeutic mechanism that should complement other modalities for treatment of SMA. ..
- Boyd P, Tu W, Shorrock H, Groen E, Carter R, Powis R, et al. Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy. PLoS Genet. 2017;13:e1006744 pubmed publisher..We conclude that global bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor neuron phenotypes in vivo. ..
- Li L, Zhou W, Fang P, Zhong Z, Xie J, Yan T, et al. Evaluation and comparison of three assays for molecular detection of spinal muscular atrophy. Clin Chem Lab Med. 2017;55:358-367 pubmed publisher..The CNVplex assay could be used to detect SMAs with complicated gene structures. The assays were reliable and could be used as alternative methods for clinical diagnosis of SMA. ..
- Custer S, Todd A, Singh N, Androphy E. Dilysine motifs in exon 2b of SMN protein mediate binding to the COPI vesicle protein ?-COP and neurite outgrowth in a cell culture model of spinal muscular atrophy. Hum Mol Genet. 2013;22:4043-52 pubmed publisher..We conclude that the interaction between SMN and ?-COP serves an important function in the growth and maintenance of motor neuron processes and may play a significant role in the pathogenesis of SMA. ..