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Review
. 2025 Jan;62(1):1282-1290.
doi: 10.1007/s12035-024-04331-0. Epub 2024 Jul 8.

DNA Damage and Chromatin Rearrangement Work Together to Promote Neurodegeneration

Harman Sharma  1 , Sushma Koirala  1 , Yee Lian Chew  1 , Anna Konopka  2
Affiliations
Review

DNA Damage and Chromatin Rearrangement Work Together to Promote Neurodegeneration

Harman Sharma et al. Mol Neurobiol. 2025 Jan.

Abstract

Neurodegenerative diseases have a complex origin and are composed of genetic and environmental factors. Both DNA damage and chromatin rearrangement are important processes that occur under pathological conditions and in neurons functioning properly. While numerous studies have demonstrated the inseparable relationship between DNA damage and chromatin organization, understanding of this relationship, especially in neurodegenerative diseases, requires further study. Interestingly, recent studies revealed that known hallmark proteins involved in neurodegenerative diseases function in both DNA damage and chromatin reorganization, and this review discusses the current knowledge of this relationship. This review focused on hallmark proteins involved in various neurodegenerative diseases, such as the microtubule-associated protein tau, TAR DNA/RNA binding protein 43 (TDP-43), superoxide dismutase 1 (SOD1), fused in sarcoma (FUS), huntingtin (HTT), α-synuclein, and β-amyloid precursor protein (APP). Hence, DNA damage and chromatin rearrangement are associated with disease mechanisms in distinct neurodegenerative diseases. Targeting common modulators of DNA repair and chromatin reorganization may lead to promising therapies for treating neurodegeneration.

Keywords: Chromatin rearrangement; DNA damage; Hallmark proteins; Neurodegeneration.

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Conflict of interest statement

Declarations. Ethics Approval: Not applicable Consent to Participate: Not applicable Consent for Publication: Not applicable Competing interests: The authors have no relevant financial or nonfinancial interests to disclose.

Figures

Illustration 1
Illustration 1
A simplified illustration of the interplay between DNA damage and chromatin organization in neurodegeneration. DNA damage and chromatin reorganization are inseparable processes. A number of proteins associated with various neurodegenerative diseases impact both processes during ongoing DNA damage, binding together distinct disease mechanisms. TDP-43, TAR DNA/RNA binding protein 43; FUS, fused in sarcoma; HT, Huntingtin; α-syn, α-synuclein; APP, β-amyloid precursor protein; tau, a microtubule-associated protein
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