Modeling spinal muscular atrophy in Drosophila links Smn to FGF signaling

Spinal muscular atrophy (SMA), a devastating neurodegenerative disorder characterized by motor neuron loss and muscle atrophy, has been linked to mutations in the Survival Motor Neuron (SMN) gene. Based on an SMA model we developed in Drosophila, which displays features that are analogous to the human pathology and vertebrate SMA models, we functionally linked the fibroblast growth factor (FGF) signaling pathway to the Drosophila homologue of SMN, Smn. Here, we characterize this relationship and demonstrate that Smn activity regulates the expression of FGF signaling components and thus FGF signaling. Furthermore, we show that alterations in FGF signaling activity are able to modify the neuromuscular junction defects caused by loss of Smn function and that muscle-specific activation of FGF is sufficient to rescue Smn-associated abnormalities.

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What Genetics Has Told Us and How It Can Inform Future Experiments for Spinal Muscular Atrophy, a Perspective

International Journal of Molecular Sciences ◽

10.3390/ijms22168494 ◽

2021 ◽

Vol 22 (16) ◽

pp. 8494

Author(s):

Anton J. Blatnik ◽

Vicki L. McGovern ◽

Arthur H. M. Burghes

Keyword(s):

Spinal Muscular Atrophy ◽

Motor Neuron ◽

Neurodegenerative Disorder ◽

Muscular Atrophy ◽

Survival Motor Neuron ◽

Cellular Functions ◽

Neuron Loss ◽

Protein Levels ◽

Motor Neuron Loss ◽

Smn Protein

Proximal spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder characterized by motor neuron loss and subsequent atrophy of skeletal muscle. SMA is caused by deficiency of the essential survival motor neuron (SMN) protein, canonically responsible for the assembly of the spliceosomal small nuclear ribonucleoproteins (snRNPs). Therapeutics aimed at increasing SMN protein levels are efficacious in treating SMA. However, it remains unknown how deficiency of SMN results in motor neuron loss, resulting in many reported cellular functions of SMN and pathways affected in SMA. Herein is a perspective detailing what genetics and biochemistry have told us about SMA and SMN, from identifying the SMA determinant region of the genome, to the development of therapeutics. Furthermore, we will discuss how genetics and biochemistry have been used to understand SMN function and how we can determine which of these are critical to SMA moving forward.

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Spinal Muscular Atrophy Type B Awareness and Symptoms Prediction Using 3D Segmentation Process in MRI Images

International Journal of Scientific Research in Computer Science Engineering and Information Technology ◽

10.32628/cseit195142 ◽

2019 ◽

pp. 312-318

Author(s):

V. Manochithra ◽

G. Sumithra

Keyword(s):

Spinal Muscular Atrophy ◽

Motor Neuron ◽

Muscular Atrophy ◽

Homozygous Deletion ◽

Survival Motor Neuron ◽

Molecular Testing ◽

Prevention Measures ◽

Neuron Loss ◽

Motor Neuron Loss ◽

Smn Protein

Spinal muscular atrophy (SMA) describes a group of disorders associated with spinal motor neuron loss. In this review we provide an update regarding the most common form of SMA, proximal or 5q SMA, and discuss the contemporary approach to diagnosis and treatment. Electromyography and muscle biopsy features of denervation were once the basis for diagnosis, but molecular testing for homozygous deletion or mutation of the SMN1 gene allows efficient and specific diagnosis. In combination with loss of SMN1, patients retain variable numbers of copies of a second similar gene, SMN2, which produce reduced levels of the survival motor neuron (SMN) protein that are insufficient for normal motor neuron function. Despite the fact that the understanding of how ubiquitous reduction of SMN protein leads to motor neuron loss remains incomplete, several promising therapeutics are now being tested in early phase clinical trials. This proposed model investigates the symptoms and scans readings from the initial MRI scan images of babies with mutation progress and SMN proteins formation benchmark values for this particular disorder SMA and further this segmented parameters are acquitted into the K-means clustering technique that predict the report with the disorder symptoms with MSE (mean square error) values that helps the babies in future to take prevention measures to overcome this problem.

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Spinal Muscular Atrophy and Progressive Myoclonic Epilepsy: A Rare Association

Journal of Neurosciences in Rural Practice ◽

10.1055/s-0040-1721543 ◽

2021 ◽

Vol 12 (01) ◽

pp. 210-212

Author(s):

Divya M. Radhakrishnan ◽

Ritu Shree ◽

Govind Madhaw ◽

Rajat Manchanda ◽

Anita Mahadevan ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Motor Neuron ◽

Muscular Atrophy ◽

Survival Motor Neuron ◽

Myoclonic Epilepsy ◽

Motor Symptoms ◽

Rare Association ◽

Smn Gene ◽

Progressive Myoclonic Epilepsy ◽

Progressive Weakness

AbstractThe association of spinal muscular atrophy (SMA) with progressive myoclonic epilepsy, also known as “SMA plus,” is a unique syndrome linked to non-survival motor neuron (non-SMN) genes. The disease starts in childhood with progressive weakness and atrophy of muscles; myoclonic epilepsy develops during later childhood, after the onset of motor symptoms. In this report, we describe a case of SMN gene unrelated SMA and myoclonic epilepsy, supported by electrophysiological and neuropathological evidences.

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