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Human Genetics

, Volume 122, Issue 6, pp 635–643 | Cite as

Induction of full-length survival motor neuron by polyphenol botanical compounds

  • Mary S. Sakla
  • Christian L. Lorson
Original Investigation

Abstract

The loss of survival motor neuron-1 (SMN1) is responsible for the development of the neurodegenerative disorder spinal muscular atrophy (SMA). A nearly identical copy of SMN1 is present on the same chromosomal region called SMN2. While SMN2 encodes a normal SMN protein, the majority of SMN2-derived transcripts are alternatively spliced, resulting in a truncated protein that lacks the 16 amino acids encoded by SMN exon 7. Numerous studies have shown that the SMN2-derived protein product, called SMNΔ7, is unstable and dysfunctional. Therefore, identifying molecules that stimulate full-length SMN expression from the SMN2 gene could lead to the development of effective therapies for a broad range of SMA patient populations. Polyphenol compounds have been shown to provide benefit in varied genetic disease contexts. For example, epigallocatechin galate (EGCG) was found to correct aberrant alternative mRNA splicing in familiar dysautonomia (FD). A series of polyphenols were screened and a subset was shown to increase full-length SMN expression from SMN2. Curcumin, EGCG, and resveratrol increased exon 7 inclusion of SMN2 transcripts in transient reporter assays. In SMA patient fibroblasts, these compounds stimulated the production of full-length SMN RNA and protein as well as the formation of SMN-containing nuclear gems. Collectively, these compounds elevated total SMN concentrations in SMA patient fibroblasts, potentially through the modulation of SMN2 exon 7 alternative splicing.

Keywords

Curcumin Resveratrol EGCG Spinal Muscular Atrophy Spinal Muscular Atrophy Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was funded by grants from the Muscular Dystrophy Association (C.L.L.) and the National Institutes of Health (C.L.L, R01 NS41584; R01 HD054413).

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  1. 1.Department of Veterinary Pathobiology, Life Sciences CenterUniversity of MissouriColumbiaUSA

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