Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Oct 18;14(10):1324.
doi: 10.3390/biom14101324.

Targeting Protein Aggregation in ALS

Michele Perni  1   2 , Benedetta Mannini  3   4
Affiliations
Review

Targeting Protein Aggregation in ALS

Michele Perni et al. Biomolecules. .

Abstract

Proteinopathies involve the abnormal accumulation of specific proteins. Maintaining the balance of the proteome is a finely regulated process managed by a complex network of cellular machinery responsible for protein synthesis, folding, and degradation. However, stress and ageing can disrupt this balance, leading to widespread protein aggregation. Currently, several therapies targeting protein aggregation are in clinical trials for ALS. These approaches mainly focus on two strategies: addressing proteins that are prone to aggregation due to mutations and targeting the cellular mechanisms that maintain protein homeostasis to prevent aggregation. This review will cover these emerging drugs. Advances in ALS research not only offer hope for better outcomes for ALS patients but also provide valuable insights and methodologies that can benefit the broader field of neurodegenerative disease drug discovery.

Keywords: amyotrophic lateral sclerosis; clinical trials; drug discovery; inflammation; neurodegeneration; protein aggregation; protein homeostasis; therapeutics.

PubMed Disclaimer

Conflict of interest statement

Author Michele Perni was employed by the company Baz-Therapeutics Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Drugs targeting protein aggregation in ALS categorized according to their mode of action.
See this image and copyright information in PMC

References

    1. Cox D., Raeburn C., Sui X., Hatters D.M. Protein Aggregation in Cell Biology: An Aggregomics Perspective of Health and Disease. Semin. Cell Dev. Biol. 2020;99:40–54. doi: 10.1016/j.semcdb.2018.05.003. - DOI - PubMed
    1. Hartl F.U., Bracher A., Hayer-Hartl M. Molecular Chaperones in Protein Folding and Proteostasis. Nature. 2011;475:324–332. doi: 10.1038/nature10317. - DOI - PubMed
    1. Vecchi G., Sormanni P., Mannini B., Vandelli A., Tartaglia G.G., Dobson C.M., Hartl F.U., Vendruscolo M. Proteome-Wide Observation of the Phenomenon of Life on the Edge of Solubility. Proc. Natl. Acad. Sci. USA. 2020;117:1015–1020. doi: 10.1073/pnas.1910444117. - DOI - PMC - PubMed
    1. Sui X., Pires D.E.V., Ormsby A.R., Cox D., Nie S., Vecchi G., Vendruscolo M., Ascher D.B., Reid G.E., Hatters D.M. Widespread Remodeling of Proteome Solubility in Response to Different Protein Homeostasis Stresses. Proc. Natl. Acad. Sci. USA. 2020;117:2422–2431. doi: 10.1073/pnas.1912897117. - DOI - PMC - PubMed
    1. Walther D.M., Kasturi P., Zheng M., Pinkert S., Vecchi G., Ciryam P., Morimoto R.I., Dobson C.M., Vendruscolo M., Mann M., et al. Widespread Proteome Remodeling and Aggregation in Aging C. Elegans. Cell. 2015;161:919–932. doi: 10.1016/j.cell.2015.03.032. - DOI - PMC - PubMed

MeSH terms

Substances

LinkOut - more resources