Skip to main content
placeholder image

Proteostasis impairment and ALS

Journal Article


Abstract


  • Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disease that results from the loss of both upper and lower motor neurons. It is the most common motor neuron disease and currently has no effective treatment. There is mounting evidence to suggest that disturbances in proteostasis play a significant role in ALS pathogenesis. Proteostasis is the maintenance of the proteome at the right level, conformation and location to allow a cell to perform its intended function. In this review, we present a thorough synthesis of the literature that provides evidence that genetic mutations associated with ALS cause imbalance to a proteome that is vulnerable to such pressure due to its metastable nature. We propose that the mechanism underlying motor neuron death caused by defects in mRNA metabolism and protein degradation pathways converges on proteostasis dysfunction. We propose that the proteostasis network may provide an effective target for therapeutic development in ALS.

Publication Date


  • 2022

Citation


  • Lambert-Smith, I. A., Saunders, D. N., & Yerbury, J. J. (2022). Proteostasis impairment and ALS. Progress in Biophysics and Molecular Biology, 174, 3-27. doi:10.1016/j.pbiomolbio.2022.06.001

Scopus Eid


  • 2-s2.0-85133363566

Web Of Science Accession Number


Start Page


  • 3

End Page


  • 27

Volume


  • 174

Abstract


  • Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal neurodegenerative disease that results from the loss of both upper and lower motor neurons. It is the most common motor neuron disease and currently has no effective treatment. There is mounting evidence to suggest that disturbances in proteostasis play a significant role in ALS pathogenesis. Proteostasis is the maintenance of the proteome at the right level, conformation and location to allow a cell to perform its intended function. In this review, we present a thorough synthesis of the literature that provides evidence that genetic mutations associated with ALS cause imbalance to a proteome that is vulnerable to such pressure due to its metastable nature. We propose that the mechanism underlying motor neuron death caused by defects in mRNA metabolism and protein degradation pathways converges on proteostasis dysfunction. We propose that the proteostasis network may provide an effective target for therapeutic development in ALS.

Publication Date


  • 2022

Citation


  • Lambert-Smith, I. A., Saunders, D. N., & Yerbury, J. J. (2022). Proteostasis impairment and ALS. Progress in Biophysics and Molecular Biology, 174, 3-27. doi:10.1016/j.pbiomolbio.2022.06.001

Scopus Eid


  • 2-s2.0-85133363566

Web Of Science Accession Number


Start Page


  • 3

End Page


  • 27

Volume


  • 174