Key role of SMN/SYNCRIP and RNA-Motif 7 in spinal muscular atrophy: RNA-Seq and motif analysis of human motor neurons

ABSTRACT:Motor neuron diseases selectively produce degeneration and death of motor neurons; the pathogenesis of these disorders and the specificity for this population of neurons are unknown. Hereditary Canine Spinal Muscular Atrophy produces a lower motor neuron disease which is clinically and pathologically similar to human motor neuron disease: motor neurons dysfunction and degenerate. The canine model provides an opportunity to investigate early stages of disease when there are viable motor neurons still present and might be responsive to a variety of therapeutic interventions. The canine disease, like the human disease, is inherited as an autosomal dominant. The extensive canine pedigree of more than 200 characterized individuals permits genetic analysis using syntenic linkage techniques which may identify a marker for the canine trait and provide insights into homologous regions for study in human kindreds.

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Spinal muscular atrophy phenotype is ameliorated in human motor neurons by SMN increase via different novel RNA therapeutic approaches

Scientific Reports ◽

10.1038/srep11746 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 25

Author(s):

Monica Nizzardo ◽

Chiara Simone ◽

Sara Dametti ◽

Sabrina Salani ◽

Gianna Ulzi ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Motor Neurons ◽

Muscular Atrophy ◽

Therapeutic Approaches ◽

Human Motor

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Examine the role of minor splicing pathway in spinal muscular atrophy

10.32469/10355/48228 ◽

2014 ◽

Author(s):

◽

Pei-Fen Yen

Keyword(s):

Spinal Muscular Atrophy ◽

Motor Neurons ◽

Muscular Atrophy ◽

Autosomal Recessive Disorder ◽

Potential Effect ◽

Survival Motor Neuron ◽

Disease Phenotypes ◽

Peak Weight ◽

Central Synapses

Spinal Muscular Atrophy (SMA) is an autosomal recessive disorder mainly caused by deletions or mutations of one gene, Survival Motor Neuron (SMN). SMN is crucial in splicing processes for proper gene expression. Previous studies showed a significant decrease in the levels of minor splicing (U12 intron) snRNPs in SMA mice and a restoration of a U12 intron-containing gene partially rescued disease phenotypes in SMA animal models. Here we utilized viral delivery system to investigate the potential effect of increasing minor splicing snRNAs on SMN deficiency. We introduced minor splicing snRNAs, human U11 and U12, or human U11, U12 with U4atac to the well-characterized SMA mice. Our treatment prolonged survival and increased percent peak weight gain. The motor function was improved however NMJ pathology was largely uncorrected. Nonetheless, the increment of minor splicing snRNAs maintained the number of central synapses on motor neurons. Furthermore, no changes in SMN expression after the treatment indicated that increasing minor splicing snRNAs partially benefits disease phenotypes independent to SMN expression in SMA mice. Furthermore, defects in U12-intron splicing events were partially corrected for U12 intron-containing SMN target gene, Stasimon, reiterating the improvement of minor splicing in SMA mice. Taken together, our results showed the restoration of minor splicing snRNAs partially ameliorates SMN deficiency caused phenotypes, indicating that U12-dependent minor splicing event is responsible for the disease progress of SMA.

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Tissue-specific models of spinal muscular atrophy confirm a critical role of SMN in motor neurons from embryonic to adult stages

Human Molecular Genetics ◽

10.1093/hmg/ddw044 ◽

2016 ◽

Vol 25 (9) ◽

pp. 1728-1738 ◽

Cited By ~ 14

Author(s):

Angela S. Laird ◽

Nikolce Mackovski ◽

Silke Rinkwitz ◽

Thomas S. Becker ◽

Jean Giacomotto

Keyword(s):

Spinal Muscular Atrophy ◽

Motor Neurons ◽

Muscular Atrophy ◽

Critical Role ◽

Tissue Specific

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AN AYURVEDIC MANAGEMENT OF SPINAL MUSCULAR ATROPHY (SMA) – A CASE STUDY

November 2020 - International Ayurvedic Medical Journal ◽

10.46607/iamj4309112021 ◽

2021 ◽

Vol 9 (11) ◽

pp. 2897-2902

Author(s):

Raheena B ◽

Shaila Borannavar ◽

Ananta S Desai

Keyword(s):

Spinal Muscular Atrophy ◽

Motor Neurons ◽

Autosomal Recessive ◽

Muscular Atrophy ◽

Genetic Disorder ◽

The Body ◽

Erect Posture ◽

Smn1 Gene ◽

Autosomal Recessive Pattern

Spinal Muscular Atrophy (SMA) is the second leading genetic disorder inherited in the autosomal recessive pattern due to the absence of the SMN1 gene characterized by loss of motor neurons and progressive muscle wasting, often leading to dependent life and decreased life span. In Ayurveda, this condition can be considered as Kulaja Vyadhi wherein the patient’s Mamsa and Snayu is affected by Vata. This can be regarded as Mamsa-Snayugata Sarvanga Vata. It is said that Prakruta Vata dosha is the life, it is the strength, it is the sustainer of the body, it holds the body and life together. If it is Vikruta it produces Sankocha, Khanja, Kubjatva, Pangutva, Khalli and Soshana of Anga. So, in this disease aggravated Vata does the vitiation of Mamsa and Snayu thus leading to Soshana of both, resulting in Stambha, Nischalikarana of Avayava. A 21years female patient was admitted to our I.P.D with c/o of reduced strength in all four limbs leading to the inability to walk and to maintain erect posture during standing and sitting positions. Based on Ayurvedic principles the patient was initially subjected to Avaranahara Chikitsa followed by Brimhana line of management. Keywords: Mamsagata vata, Snayugata vata, Sarvanga vata, Spinal muscular atrophy (SMA)

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Multifaceted roles of microRNAs: From motor neuron generation in embryos to degeneration in spinal muscular atrophy

eLife ◽

10.7554/elife.50848 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 2

Author(s):

Tai-Heng Chen ◽

Jun-An Chen

Keyword(s):

Nervous System ◽

Neurodegenerative Diseases ◽

Spinal Muscular Atrophy ◽

Motor Neuron ◽

Motor Neurons ◽

Muscular Atrophy ◽

Cell Types ◽

Spinal Motor Neurons ◽

Potential Applications ◽

The Central Nervous System

Two crucial questions in neuroscience are how neurons establish individual identity in the developing nervous system and why only specific neuron subtypes are vulnerable to neurodegenerative diseases. In the central nervous system, spinal motor neurons serve as one of the best-characterized cell types for addressing these two questions. In this review, we dissect these questions by evaluating the emerging role of regulatory microRNAs in motor neuron generation in developing embryos and their potential contributions to neurodegenerative diseases such as spinal muscular atrophy (SMA). Given recent promising results from novel microRNA-based medicines, we discuss the potential applications of microRNAs for clinical assessments of SMA disease progression and treatment.

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