Possible pathogenic role of muscle cell dysfunction in motor neuron death in spinal muscular atrophy

2002 ◽  
Vol 25 (5) ◽  
pp. 700-708 ◽  
Author(s):  
S�verine Guettier-Sigrist ◽  
B�n�dicte Hugel ◽  
Gilliane Coupin ◽  
Jean-Marie Freyssinet ◽  
Philippe Poindron ◽  
...  
Keyword(s):  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscle Cell ◽  
Muscular Atrophy ◽  
Pathogenic Role ◽  
Neuron Death ◽  
Cell Dysfunction ◽  
Motor Neuron Death

scholarly journals Stasimon Contributes to the Loss of Sensory Synapses and Motor Neuron Death in a Mouse Model of Spinal Muscular Atrophy

2019 ◽  
Author(s):  
Christian Simon ◽  
Meaghan Van Alstyne ◽  
Francesco Lotti ◽  
Elena Bianchetti ◽  
Sarah Tisdale ◽  
...  
Keyword(s):  
Mouse Model ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Neuron Death ◽  
Motor Neuron Death

scholarly journals Dysregulation of Mdm2 and Mdm4 alternative splicing underlies motor neuron death in spinal muscular atrophy

2018 ◽  
Vol 32 (15-16) ◽  
pp. 1045-1059 ◽  
Author(s):  
Meaghan Van Alstyne ◽  
Christian M. Simon ◽  
S. Pablo Sardi ◽  
Lamya S. Shihabuddin ◽  
George Z. Mentis ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Neuron Death ◽  
Motor Neuron Death

scholarly journals Stasimon Contributes to the Loss of Sensory Synapses and Motor Neuron Death in a Mouse Model of Spinal Muscular Atrophy

Cell Reports ◽  
2019 ◽  
Vol 29 (12) ◽  
pp. 3885-3901.e5 ◽  
Author(s):  
Christian M. Simon ◽  
Meaghan Van Alstyne ◽  
Francesco Lotti ◽  
Elena Bianchetti ◽  
Sarah Tisdale ◽  
...  
Keyword(s):  
Mouse Model ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Neuron Death ◽  
Motor Neuron Death

scholarly journals Teaching an old drug new tricks: repositioning strategies for spinal muscular atrophy

2019 ◽  
Vol 14 (3) ◽  
pp. FNL25
Author(s):  
Joseph M Hoolachan ◽  
Emma R Sutton ◽  
Melissa Bowerman
Keyword(s):  
Spinal Muscular Atrophy ◽  
Muscular Atrophy ◽  
Genetic Therapy ◽  
Neuron Death ◽  
Muscle Disorders ◽  
Motor Neuron Death ◽  
Smn Gene ◽  
New Treatments ◽  
Spinal Cord Motor Neuron ◽  
Maximal Benefit

Spinal muscular atrophy (SMA) is a childhood disorder caused by loss of the SMN gene. Pathological hallmarks are spinal cord motor neuron death, neuromuscular junction dysfunction and muscle atrophy. The first SMN genetic therapy was recently approved and other SMN-dependent treatments are not far behind. However, not all SMA patients will reap their maximal benefit due to limited accessibility, high costs and differential effects depending on timing of administration and disease severity. The repurposing of commercially available drugs is an interesting strategy to ensure more rapid and less expensive access to new treatments. In this mini-review, we will discuss the potential and relevance of repositioning drugs currently used for neurodegenerative, neuromuscular and muscle disorders for SMA.

scholarly journals Delayed and selective motor neuron death after transient spinal cord ischemia: A role of apoptosis?

1998 ◽  
Vol 115 (6) ◽  
pp. 1310-1315 ◽  
Author(s):  
Masahiro Sakurai ◽  
Takeshi Hayashi ◽  
Koji Abe ◽  
Mitsuaki Sadahiro ◽  
Koichi Tabayashi
Keyword(s):  
Spinal Cord ◽  
Motor Neuron ◽  
Spinal Cord Ischemia ◽  
Neuron Death ◽  
Motor Neuron Death

scholarly journals Revisiting the role of mitochondria in spinal muscular atrophy

2021 ◽  
Author(s):  
Rachel James ◽  
Helena Chaytow ◽  
Leire M. Ledahawsky ◽  
Thomas H. Gillingwater
Keyword(s):  
Nervous System ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Neurodegenerative Disorders ◽  
Autosomal Recessive ◽  
Muscular Atrophy ◽  
Survival Motor Neuron ◽  
Clinical Severity ◽  
Motor Neuron Diseases

AbstractSpinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease of variable clinical severity that is caused by mutations in the survival motor neuron 1 (SMN1) gene. Despite its name, SMN is a ubiquitous protein that functions within and outside the nervous system and has multiple cellular roles in transcription, translation, and proteostatic mechanisms. Encouragingly, several SMN-directed therapies have recently reached the clinic, albeit this has highlighted the increasing need to develop combinatorial therapies for SMA to achieve full clinical efficacy. As a subcellular site of dysfunction in SMA, mitochondria represents a relevant target for a combinatorial therapy. Accordingly, we will discuss our current understanding of mitochondrial dysfunction in SMA, highlighting mitochondrial-based pathways that offer further mechanistic insights into the involvement of mitochondria in SMA. This may ultimately facilitate translational development of targeted mitochondrial therapies for SMA. Due to clinical and mechanistic overlaps, such strategies may also benefit other motor neuron diseases and related neurodegenerative disorders.

scholarly journals Insights of the pathophysiology of neurodegenerative diseases and the role of phytochemical compounds in its management

2021 ◽  
Vol 4 (3) ◽  
pp. 1-10
Author(s):  
Zurina Hassan ◽  
Raghava N. Sriramaneni
Keyword(s):  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
The Elderly ◽  
Common Type ◽  
Risk Category ◽  
Progressive Loss ◽  
Intellectual Abilities ◽  
Phytochemical Compounds

A neurodegenerative disease (ND) is defined as an irreversible disorder in most cases, leading to progressive loss of neurons and intellectual abilities. ND can lead to fatality in most circumstances, and the elderly above the age of sixty-five (65) constitute the major risk category. The most common type of ND includes Alzheimer's disease (AD), and Parkinson's disease (PD). Other NDs are Huntington's disease (HD), motor neuron disease (MND), spinocerebellar ataxia (SCA), spinal muscular atrophy (SMA), and prion disease. ND strikes mainly in the middle to late life incidence expected to rise as the population ages.

scholarly journals Stasimon contributes to the loss of sensory synapses and motor neuron death in a mouse model of spinal muscular atrophy

2019 ◽  
Author(s):  
Christian M. Simon ◽  
Meaghan Van Alstyne ◽  
Francesco Lotti ◽  
Elena Bianchetti ◽  
Sarah Tisdale ◽  
...  
Keyword(s):  
Mouse Model ◽  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Muscular Atrophy ◽  
Transmembrane Protein ◽  
Neuron Death ◽  
Gene Encoding ◽  
Neurodegenerative Process ◽  
Smn Protein

AbstractReduced expression of the SMN protein causes spinal muscular atrophy (SMA) – an inherited neurodegenerative disease characterized by multiple synaptic deficits and motor neuron loss. Here, we show that AAV9-mediated delivery of Stasimon – a gene encoding an ER-resident transmembrane protein regulated by SMN – improves motor function in a mouse model of SMA through multiple mechanisms. In proprioceptive neurons of SMA mice, Stasimon overexpression prevents the loss of afferent synapses on motor neurons and enhances sensory-motor neurotransmission. In SMA motor neurons, Stasimon suppresses the neurodegenerative process by selectively reducing phosphorylation but not upregulation of the tumor suppressor p53, both of which are converging events required to trigger neuronal death. We further show that Stasimon deficiency synergizes with SMA-related mechanisms of p53 upregulation to induce phosphorylation of p53. These findings identify Stasimon dysfunction induced by SMN deficiency as an upstream driver of cellular pathways that lead to synaptic loss and motor neuron degeneration, revealing a dual contribution of Stasimon to motor circuit pathology in SMA.

Spinal Muscular Atrophy and the Antiapoptotic Role of Survival of Motor Neuron (SMN) Protein

2013 ◽  
Vol 47 (2) ◽  
pp. 821-832 ◽  
Author(s):  
Ryan S. Anderton ◽  
Bruno P. Meloni ◽  
Frank L. Mastaglia ◽  
Sherif Boulos
Keyword(s):  
Spinal Muscular Atrophy ◽  
Motor Neuron ◽  
Muscular Atrophy ◽  
Smn Protein ◽  
Survival Of Motor Neuron

scholarly journals Role of EphA4 in Mediating Motor Neuron Death in MND

2021 ◽  
Vol 22 (17) ◽  
pp. 9430
Author(s):  
Jing Zhao ◽  
Claire H. Stevens ◽  
Andrew W. Boyd ◽  
Lezanne Ooi ◽  
Perry F. Bartlett
Keyword(s):  
Cell Death ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Motor Neurons ◽  
Functional Outcomes ◽  
Underlying Mechanism ◽  
Neuron Death ◽  
Pathological Characteristics ◽  
Motor Neuron Death

Motor neuron disease (MND) comprises a group of fatal neurodegenerative diseases with no effective cure. As progressive motor neuron cell death is one of pathological characteristics of MND, molecules which protect these cells are attractive therapeutic targets. Accumulating evidence indicates that EphA4 activation is involved in MND pathogenesis, and inhibition of EphA4 improves functional outcomes. However, the underlying mechanism of EphA4’s function in MND is unclear. In this review, we first present results to demonstrate that EphA4 signalling acts directly on motor neurons to cause cell death. We then review the three most likely mechanisms underlying this effect.

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