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Review
. 2023 Nov 3;11(11):2967.
doi: 10.3390/biomedicines11112967.

Characteristics of Sensory Neuron Dysfunction in Amyotrophic Lateral Sclerosis (ALS): Potential for ALS Therapy

Soju Seki  1 , Yoshihiro Kitaoka  1 , Sou Kawata  1 , Akira Nishiura  1 , Toshihiro Uchihashi  1 , Shin-Ichiro Hiraoka  1 , Yusuke Yokota  1 , Emiko Tanaka Isomura  1 , Mikihiko Kogo  1 , Susumu Tanaka  1
Affiliations
Review

Characteristics of Sensory Neuron Dysfunction in Amyotrophic Lateral Sclerosis (ALS): Potential for ALS Therapy

Soju Seki et al. Biomedicines. .

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterised by the progressive degeneration of motor neurons, resulting in muscle weakness, paralysis, and, ultimately, death. Presently, no effective treatment for ALS has been established. Although motor neuron dysfunction is a hallmark of ALS, emerging evidence suggests that sensory neurons are also involved in the disease. In clinical research, 30% of patients with ALS had sensory symptoms and abnormal sensory nerve conduction studies in the lower extremities. Peroneal nerve biopsies show histological abnormalities in 90% of the patients. Preclinical research has reported several genetic abnormalities in the sensory neurons of animal models of ALS, as well as in motor neurons. Furthermore, the aggregation of misfolded proteins like TAR DNA-binding protein 43 has been reported in sensory neurons. This review aims to provide a comprehensive description of ALS-related sensory neuron dysfunction, focusing on its clinical changes and underlying mechanisms. Sensory neuron abnormalities in ALS are not limited to somatosensory issues; proprioceptive sensory neurons, such as MesV and DRG neurons, have been reported to form networks with motor neurons and may be involved in motor control. Despite receiving limited attention, sensory neuron abnormalities in ALS hold potential for new therapies targeting proprioceptive sensory neurons.

Keywords: ALS mouse model; amyotrophic lateral sclerosis (ALS); dorsal root ganglion (DRG); mesencephalic trigeminal nucleus (MesV); neurodegeneration; sensory neuron.

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Conflict of interest statement

The authors declare no competing interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
This review focuses on sensory neuron abnormalities in amyotrophic lateral sclerosis (ALS). As various sensory neuron abnormalities have been reported in studies using animal models, this review proposes a novel therapeutic strategy for ALS by correcting the proprioceptive sensory neuron abnormalities in patients with ALS.
Figure 2
Figure 2
Therapeutic strategies for the cytoplasmic deposition of TDP-43 using AAV vectors. Cytoplasmic deposition of TDP-43 in ALS has been suggested to be due to abnormal RNA metabolism. Attempts to ameliorate TDP-43 cytoplasmic deposition via gene therapy using AAV vectors have been investigated and may be applicable to the treatment of DRGs.
Figure 3
Figure 3
Therapeutic strategies for the correction of sodium ion channels via neuropeptides. Neuropeptides such as orexin and NPY may increase MesV sodium current and improve firing activity in ALS with reduced sodium currents.
See this image and copyright information in PMC

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References

    1. Al-Chalabi A., Hardiman O. The Epidemiology of ALS: A Conspiracy of Genes, Environment and Time. Nat. Rev. Neurol. 2013;9:617–628. doi: 10.1038/nrneurol.2013.203. - DOI - PubMed
    1. Riancho J., Gonzalo I., Ruiz-Soto M., Berciano J. Why Do Motor Neurons Degenerate? Actualization in the Pathogenesis of Amyotrophic Lateral Sclerosis. Neurología. 2019;34:27–37. doi: 10.1016/j.nrl.2015.12.001. - DOI - PubMed
    1. Tanaka M., Toldi J., Vécsei L. Exploring the Etiological Links behind Neurodegenerative Diseases: Inflammatory Cytokines and Bioactive Kynurenines. Int. J. Mol. Sci. 2020;21:2431. doi: 10.3390/ijms21072431. - DOI - PMC - PubMed
    1. Tanaka M., Szabó Á., Spekker E., Polyák H., Tóth F., Vécsei L. Mitochondrial Impairment: A Common Motif in Neuropsychiatric Presentation? The Link to the Tryptophan–Kynurenine Metabolic System. Cells. 2022;11:2607. doi: 10.3390/cells11162607. - DOI - PMC - PubMed
    1. Bunton-Stasyshyn R.K., Saccon R.A., Fratta P., Fisher E.M. SOD1 Function and Its Implications for Amyotrophic Lateral Sclerosis Pathology: New and Renascent Themes. Neuroscientist. 2015;21:519–529. doi: 10.1177/1073858414561795. - DOI - PubMed

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