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Feb 19, 2021;10 (2):

Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases.

Swapnil Gupta, Panpan You, Tanima SenGupta, Hilde Nilsen, Kulbhushan Sharma
Author Information
  1. Swapnil Gupta: Department of Clinical Molecular Biology, University of Oslo, 0318 Oslo, Norway.
  2. Panpan You: Department of Clinical Molecular Biology, University of Oslo, 0318 Oslo, Norway.
  3. Tanima SenGupta: Department of Clinical Molecular Biology, University of Oslo, 0318 Oslo, Norway.
  4. Hilde Nilsen: Department of Clinical Molecular Biology, University of Oslo, 0318 Oslo, Norway.
  5. Kulbhushan Sharma: Department of Clinical Molecular Biology, University of Oslo, 0318 Oslo, Norway. ORCID
PMID: 33669593 DOI: 10.3390/biology10020163

Abstract

Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). Dysregulation or dysfunction of DDR is also proposed to contribute to more common NDDs, such as Parkinson's disease (PD), Alzheimer's disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we present mechanisms that link DDR with neurodegeneration in rare NDDs caused by defects in the DDR and discuss the relevance for more common age-related neurodegenerative diseases. Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. We compare the strengths and limitations of established model systems to model human NDDs, ranging from and mouse models towards advanced stem cell-based 3D models.

Keywords

ALS Alzheimer DNA damage response PARP Parkinson cGAS-STING neurodegeneration neuroinflammation oxidative stress

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