Emerging concepts underlying selective neuromuscular dysfunction in infantile-onset spinal muscular atrophy

Infantile-onset spinal muscular atrophy is the quintessential example of a disorder characterized by a predominantly neurodegenerative phenotype that nevertheless stems from perturbations in a housekeeping protein. Resulting from low levels of the Survival of Motor Neuron (SMN) protein, spinal muscu...

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Bibliographic Details
Published in:Neural regeneration research 2021-10, Vol.16 (10), p.1978-1984
Main Authors: Gollapalli, Kishore, Kim, Jeong-Ki, Monani, Umrao
Format: Article
Language:English
Subjects:
Atrophy
Atrophy, Muscular
Care and treatment
Cellular proteins
Diagnosis
Genetic aspects
Health aspects
Methods
Molecular diagnostic techniques
motor neuron
neurodegeneration
neuromuscular
spinal muscular atrophy
splicing
Neuromuscular diseases
Review
Spinal diseases
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Summary:Infantile-onset spinal muscular atrophy is the quintessential example of a disorder characterized by a predominantly neurodegenerative phenotype that nevertheless stems from perturbations in a housekeeping protein. Resulting from low levels of the Survival of Motor Neuron (SMN) protein, spinal muscular atrophy manifests mainly as a lower motor neuron disease. Why this is so and whether other cell types contribute to the classic spinal muscular atrophy phenotype continue to be the subject of intense investigation and are only now gaining appreciation. Yet, what is emerging is sometimes as puzzling as it is instructive, arguing for a careful re-examination of recent study outcomes, raising questions about established dogma in the field and making the case for a greater focus on milder spinal muscular atrophy models as tools to identify key mechanisms driving selective neuromuscular dysfunction in the disease. This review examines the evidence for novel molecular and cellular mechanisms that have recently been implicated in spinal muscular atrophy, highlights breakthroughs, points out caveats and poses questions that ought to serve as the basis of new investigations to better understand and treat this and other more common neurodegenerative disorders.
ISSN:1673-5374
1876-7958
DOI:10.4103/1673-5374.308073