survival of motor neuron 2 protein

Summary

Summary: An SMN complex protein that is closely-related to SURVIVAL OF MOTOR NEURON 1 PROTEIN. In humans, the protein is encoded by an often duplicated gene found near the inversion CENTEROMERE of a large inverted region of CHROMOSOME 5.

Top Publications

  1. Wan L, Dreyfuss G. Splicing-Correcting Therapy for SMA. Cell. 2017;170:5 pubmed publisher
    ..Antisense treatment to SMN2 intron7-splicing silencer (ISS) improves SMN expression and motor function. To view this Bench to Bedside, open or download the PDF. ..
  2. 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. ..
  3. Pinard E, Green L, Reutlinger M, Weetall M, Naryshkin N, Baird J, et al. Discovery of a Novel Class of Survival Motor Neuron 2 Splicing Modifiers for the Treatment of Spinal Muscular Atrophy. J Med Chem. 2017;60:4444-4457 pubmed publisher
    ..Optimized representative compounds modify the alternative splicing of SMN2, increase the production of full length SMN2 mRNA, and therefore levels of full length SMN protein upon oral administration in two mouse models of SMA. ..
  4. Lai J, Leman L, Ku S, Vickers C, Olsen C, Montero A, et al. Cyclic tetrapeptide HDAC inhibitors as potential therapeutics for spinal muscular atrophy: Screening with iPSC-derived neuronal cells. Bioorg Med Chem Lett. 2017;27:3289-3293 pubmed publisher
    ..Our study identifies new potential HDACi therapeutics for SMA screened using a disease-relevant SMA neuronal cellular model. ..
  5. 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. ..
  6. Cherry J, DiDonato C, Androphy E, Calo A, Potter K, Custer S, et al. In vitro and in vivo effects of 2,4 diaminoquinazoline inhibitors of the decapping scavenger enzyme DcpS: Context-specific modulation of SMN transcript levels. PLoS ONE. 2017;12:e0185079 pubmed publisher
    ..We conclude that DAQ-DcpSi have reproducible benefit in SMA mice and a broad spectrum of biological effects in vitro and in vivo, but these are complex, context specific, and not the result of simple SMN2 transcriptional activation. ..
  7. Finkel R, Mercuri E, Darras B, Connolly A, Kuntz N, Kirschner J, et al. Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy. N Engl J Med. 2017;377:1723-1732 pubmed publisher
    ..Early treatment may be necessary to maximize the benefit of the drug. (Funded by Biogen and Ionis Pharmaceuticals; ENDEAR ClinicalTrials.gov number, NCT02193074 .). ..
  8. Tejero R, Lopez Manzaneda M, Arumugam S, Tabares L. Synaptotagmin-2, and -1, linked to neurotransmission impairment and vulnerability in Spinal Muscular Atrophy. Hum Mol Genet. 2016;25:4703-4716 pubmed publisher
    ..Together, we propose that the strong reduction of Syt2 and SV2B are key factors of the functional synaptic alteration and that the physiological downregulation of Syt1 plays a determinant role in muscle vulnerability in SMA. ..
  9. Fletcher E, Simon C, Pagiazitis J, Chalif J, Vukojicic A, Drobac E, et al. Reduced sensory synaptic excitation impairs motor neuron function via Kv2.1 in spinal muscular atrophy. Nat Neurosci. 2017;20:905-916 pubmed publisher
    ..Our results demonstrate a key role of excitatory synaptic drive in shaping the function of motor neurons during development and the contribution of its disruption to a neurodegenerative disease. ..

More Information

Publications11

  1. Gentillon C, Connell A, Kirk R, Butchbach M. The effects of C5-substituted 2,4-diaminoquinazolines on selected transcript expression in spinal muscular atrophy cells. PLoS ONE. 2017;12:e0180657 pubmed publisher
    ..This study reveals that the protective effects of 2,4-DAQs in SMA may be independent of SMN2 gene regulation. These compounds could be used in concert with a proven SMN2 inducer to develop a multi-faceted approach to treating SMA. ..
  2. Zarkov M, Stojadinović A, Sekulić S, Barjaktarović I, Perić S, Keković G, et al. Association between the SMN2 gene copy number and clinical characteristics of patients with spinal muscular atrophy with homozygous deletion of exon 7 of the SMN1 gene. Vojnosanit Pregl. 2015;72:859-63 pubmed
    ..05). In the Serbian patients with SMA, a higher SMN2 gene copy number correlated with less severe disease phenotype. A possible effect of other phenotype modifiers should not be neglected. ..