The Function of Survival Motor Neuron Complex and Its Role in Spinal Muscular Atrophy Pathogenesis

So, Byung Ran; Zhang, Z.; Dreyfuss, Gideon

doi:10.1016/b978-0-12-803685-3.00006-9

Cited by 7 publications

(10 citation statements)

References 147 publications

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“…[17][18][19] The SMN protein was first identified to play a key role in pre-mRNA splicing. [20][21][22] SMN is also involved in a number of additional key cellular pathways, most pertaining to RNA metabolism. 21,23 As such, SMN depletion has far-reaching effects on the transcriptome and cellular functions in all cell types of the body.…”

Section: Discussionmentioning

confidence: 99%

“…[20][21][22] SMN is also involved in a number of additional key cellular pathways, most pertaining to RNA metabolism. 21,23 As such, SMN depletion has far-reaching effects on the transcriptome and cellular functions in all cell types of the body. Phenotypically, the Smn 2B/mouse model shows loss of motor neurons, neuromuscular junction abnormalities, skeletal muscle atrophy, muscle weakness, weight loss, and a shortened lifespan of 25 days.…”

Section: Discussionmentioning

confidence: 99%

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SMN Depleted Mice Offer a Robust and Rapid Onset Model of Nonalcoholic Fatty Liver Disease

Deguise

Pileggi

Repentigny

et al. 2021

Cellular and Molecular Gastroenterology and Hepatology

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The Smn 2B/mice, a mouse model with reduced level of SMN protein, represent a good model of microvesicular steatohepatitis. They offer a reliable, low-cost, early-onset model to identify molecular players in the pathogenesis of NAFLD in both the adult and pediatric populations. BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is considered a health epidemic with potential devastating effects on the patients and the healthcare systems. Current preclinical models of NAFLD are invariably imperfect and generally take a long time to develop. A mouse model of survival motor neuron (SMN) depletion (Smn 2B/mice) was recently shown to develop significant hepatic steatosis in less than 2 weeks from birth. The rapid onset of fatty liver in Smn 2B/mice provides an opportunity to identify molecular markers of NAFLD. Here, we investigated whether Smn 2B/mice display typical features of NAFLD/nonalcoholic steatohepatitis (NASH). METHODS: Biochemical, histologic, electron microscopy, proteomic, and high-resolution respirometry were used.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

SMN Depleted Mice Offer a Robust and Rapid Onset Model of Nonalcoholic Fatty Liver Disease

Deguise

Pileggi

Repentigny

et al. 2021

Cellular and Molecular Gastroenterology and Hepatology

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“…SMN exhibits both cytoplasmic and nuclear subcellular localization where the protein serves several proposed functions ( Figure 2 ). SMN is a crucial component of snRNP biogenesis [ 56 , 57 , 58 ]. snRNPs are RNA–protein complexes that are critical constituents of spliceosomes, which recognize and remove introns from pre-mRNA.…”

Section: The Smn Proteinmentioning

confidence: 99%

“…At the neuromuscular synapse, SMN is involved in actin dynamics, vesicle release and recycling, and neuromuscular junction (NMJ) maturation and repair. These cellular functions of SMN have been thoroughly discussed elsewhere [ 52 , 56 , 70 , 71 , 72 , 73 , 74 ].…”

Section: Figurementioning

confidence: 99%

In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy

2021

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Until the recent development of disease-modifying therapeutics, spinal muscular atrophy (SMA) was considered a devastating neuromuscular disease with a poor prognosis for most affected individuals. Symptoms generally present during early childhood and manifest as muscle weakness and progressive paralysis, severely compromising the affected individual’s quality of life, independence, and lifespan. SMA is most commonly caused by the inheritance of homozygously deleted SMN1 alleles with retention of one or more copies of a paralog gene, SMN2, which inversely correlates with disease severity. The recent advent and use of genetically targeted therapies have transformed SMA into a prototype for monogenic disease treatment in the era of genetic medicine. Many SMA-affected individuals receiving these therapies achieve traditionally unobtainable motor milestones and survival rates as medicines drastically alter the natural progression of this disease. This review discusses historical SMA progression and underlying disease mechanisms, highlights advances made in therapeutic research, clinical trials, and FDA-approved medicines, and discusses possible second-generation and complementary medicines as well as optimal temporal intervention windows in order to optimize motor function and improve quality of life for all SMA-affected individuals.

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“…snRNP particles are RNA–protein complexes that combine with unmodified pre-mRNA and various other nuclear proteins to form a spliceosome [ 94 ]. They are essential in several aspects of nuclear posttranscriptional gene expression, including pre-mRNA splicing, telescripting and 3′ end processing of histone pre-mRNAs [ 95 ]. Each snRNP in eukaryotes consists of specific uridine-rich snRNAs, which are designated by the prefix U followed by a number and a specific set of proteins—e.g., U1snRNP.…”

Section: Rna-binding Proteins (Rbps)mentioning

confidence: 99%

Interplay of RNA-Binding Proteins and microRNAs in Neurodegenerative Diseases

Kinoshita

Kubota

Aoyama

2021

IJMS

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The number of patients with neurodegenerative diseases (NDs) is increasing, along with the growing number of older adults. This escalation threatens to create a medical and social crisis. NDs include a large spectrum of heterogeneous and multifactorial pathologies, such as amyotrophic lateral sclerosis, frontotemporal dementia, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and multiple system atrophy, and the formation of inclusion bodies resulting from protein misfolding and aggregation is a hallmark of these disorders. The proteinaceous components of the pathological inclusions include several RNA-binding proteins (RBPs), which play important roles in splicing, stability, transcription and translation. In addition, RBPs were shown to play a critical role in regulating miRNA biogenesis and metabolism. The dysfunction of both RBPs and miRNAs is often observed in several NDs. Thus, the data about the interplay among RBPs and miRNAs and their cooperation in brain functions would be important to know for better understanding NDs and the development of effective therapeutics. In this review, we focused on the connection between miRNAs, RBPs and neurodegenerative diseases.

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The Function of Survival Motor Neuron Complex and Its Role in Spinal Muscular Atrophy Pathogenesis

Cited by 7 publications

References 147 publications

SMN Depleted Mice Offer a Robust and Rapid Onset Model of Nonalcoholic Fatty Liver Disease

SMN Depleted Mice Offer a Robust and Rapid Onset Model of Nonalcoholic Fatty Liver Disease

In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy

Interplay of RNA-Binding Proteins and microRNAs in Neurodegenerative Diseases

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