Open Access: A Role for p53 in c9ALS/FTD?

Charlotte M Fare; James Shorter

doi:10.1016/j.tig.2021.01.008

Open Access: A Role for p53 in c9ALS/FTD?

Trends Genet. 2021 May;37(5):404-406. doi: 10.1016/j.tig.2021.01.008. Epub 2021 Feb 4.

Authors

Charlotte M Fare¹, James Shorter²

Affiliations

¹ Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
² Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: [email protected].

PMID: 33551183
DOI: 10.1016/j.tig.2021.01.008

Abstract

Poly(PR), a toxic dipeptide-repeat protein, translated from the pathogenic G₄C₂ repeat expansion in C9orf72, contributes to c9 amyotrophic lateral sclerosis/frontotemporal dementia (c9ALS/FTD). However, precisely how poly(PR) elicits neurodegeneration has remained unclear. Maor-Nof et al. now establish that poly(PR) remodels the neuronal epigenome to promote proapoptotic p53 activity involving PUMA, which drives neurodegeneration in several models.

Keywords: PUMA; TDP-43; c9ALS/FTD; dipeptide-repeat protein; p53; poly(PR).

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MeSH terms

Access to Information
Amyotrophic Lateral Sclerosis*
C9orf72 Protein / metabolism
Frontotemporal Dementia*
Humans
Tumor Suppressor Protein p53

Substances

C9orf72 Protein
Tumor Suppressor Protein p53