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Review
. 2016 Mar;73(5):1003-20.
doi: 10.1007/s00018-015-2106-9. Epub 2015 Dec 18.

Is spinal muscular atrophy a disease of the motor neurons only: pathogenesis and therapeutic implications?

Chiara Simone  1 , Agnese Ramirez  1 , Monica Bucchia  1 , Paola Rinchetti  1 , Hardy Rideout  2 , Dimitra Papadimitriou  2 , Diane B Re  3   4 , Stefania Corti  5
Affiliations
Review

Is spinal muscular atrophy a disease of the motor neurons only: pathogenesis and therapeutic implications?

Chiara Simone et al. Cell Mol Life Sci. 2016 Mar.

Abstract

Spinal muscular atrophy (SMA) is a genetic neurological disease that causes infant mortality; no effective therapies are currently available. SMA is due to homozygous mutations and/or deletions in the survival motor neuron 1 gene and subsequent reduction of the SMN protein, leading to the death of motor neurons. However, there is increasing evidence that in addition to motor neurons, other cell types are contributing to SMA pathology. In this review, we will discuss the involvement of non-motor neuronal cells, located both inside and outside the central nervous system, in disease onset and progression. Even if SMN restoration in motor neurons is needed, it has been shown that optimal phenotypic amelioration in animal models of SMA requires a more widespread SMN correction. It has been demonstrated that non-motor neuronal cells are also involved in disease pathogenesis and could have important therapeutic implications. For these reasons it will be crucial to take this evidence into account for the clinical translation of the novel therapeutic approaches.

Keywords: Central nervous system; Pathogenesis; Spinal muscular atrophy; Therapy.

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Figures

Fig. 1
Fig. 1
Role of astrocytes and microglia in healthy subjects and SMA patients
Fig. 2
Fig. 2
The effects of SMA on non-motor neuronal tissue
See this image and copyright information in PMC

References

    1. Monani UR. Spinal muscular atrophy: a deficiency in a ubiquitous protein; a motor neuron-specific disease. Neuron. 2005;48(6):885–896. doi: 10.1016/j.neuron.2005.12.001. - DOI - PubMed
    1. Sumner CJ. Molecular mechanisms of spinal muscular atrophy. J Child Neurol. 2007;22(8):979–989. doi: 10.1177/0883073807305787. - DOI - PubMed
    1. Zanetta C, Nizzardo M, Simone C, Monguzzi E, Bresolin N, Comi GP, Corti S. Molecular therapeutic strategies for spinal muscular atrophies: current and future clinical trials. Clin Ther. 2014;36(1):128–140. doi: 10.1016/j.clinthera.2013.11.006. - DOI - PubMed
    1. Zanetta C, Riboldi G, Nizzardo M, Simone C, Faravelli I, Bresolin N, Comi GP, Corti S. Molecular, genetic and stem cell-mediated therapeutic strategies for spinal muscular atrophy (SMA) J Cell Mol Med. 2014;18(2):187–196. doi: 10.1111/jcmm.12224. - DOI - PMC - PubMed
    1. Burghes AH, Beattie CE. Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick? Nat Rev Neurosci. 2009;10(8):597–609. doi: 10.1038/nrn2670. - DOI - PMC - PubMed

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