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Review
. 2024 Jul 22;10(15):e34963.
doi: 10.1016/j.heliyon.2024.e34963. eCollection 2024 Aug 15.

The prion-like effect and prion-like protein targeting strategy in amyotrophic lateral sclerosis

Yang Wenzhi  1   2 , Liu Xiangyi  1   2 , Fan Dongsheng  1   2
Affiliations
Review

The prion-like effect and prion-like protein targeting strategy in amyotrophic lateral sclerosis

Yang Wenzhi et al. Heliyon. .

Abstract

Pathological proteins in amyotrophic lateral sclerosis (ALS), such as superoxide dismutase 1, TAR DNA-binding protein 43, and fused in sarcoma, exhibit a prion-like pattern. All these proteins have a low-complexity domain and seeding activity in cells. In this review, we summarize the studies on the prion-like effect of these proteins and list six prion-like protein targeting strategies that we believe have potential for ALS therapy, including antisense oligonucleotides, antibody-based technology, peptide, protein chaperone, autophagy enhancement, and heteromultivalent compounds. Considering the pathological complexity and heterogeneity of ALS, we believe that the final solution to ALS therapy is most likely to be an individualized cocktail therapy, including clearance of toxicity, blockage of pathological progress, and protection of neurons.

Keywords: ALS; Prion-like; Protein.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
The six methods and their mechanism in targeting prion-like proteins. The mechanisms of the six methods against prion-like proteins are shown in this figure. ASOs block the transcription and translation process and inhibit the synthesis of pathological proteins. Antibodies can bind to pathological proteins and activate the degradation process. Peptides can bind to proteins and inhibit their aggregation. Protein chaperone can help proteins fold correctly, and prevent the production of abnormal proteins. Autophagy enhancement will enhance the protein degradation ability of cells, promoting the degradation of prion-like protein. Heteromultivalent compounds can interact with amyloid fiber, inhibit fiber formation, and promote its dissolution.
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