ArticleActa neuropathologica communications2018
Nuclear poly(ADP-ribose) activity is a therapeutic target in amyotrophic lateral sclerosis.
Article in Acta neuropathologica communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 115 citations in OpenAlex.
- Shuttle and stabilize: H1.2-FUS complex in amyotrophic lateral sclerosis pathogenesis.Neural regeneration research · 2026Article
- TDP-43 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- A human Staufen1 BAC transgenic mouse exhibits abnormal autophagy and neurodegeneration across the central nervous system.Cell death & disease · 2026Article
- Poly(ADP-ribose) (PAR) exhibits ion-dependent structural properties distinct from RNA.Nucleic acids research · 2026Article
- Aberrant CDK4/6-driven cell-cycle reentry drives neuronal loss and defines a therapeutic target in C9orf72 ALS/FTD.iScience · 2026Article
- Non-canonical cell death in neurodegeneration: emerging mechanisms and therapeutic Frontiers.Apoptosis : an international journal on programmed cell death · 2026Review
- Epigenetic consequences of DNA damage.Molecular cell · 2026Review
- Aberrant NSUN1 activity connects mLife science alliance · 2026Article
- NEDD8, stress granules, and amyotrophic lateral sclerosis: unveiling the therapeutic potential of the NEDP1 protease.Essays in biochemistry · 2025Review
- Tipping the PARylation scale: Dysregulation of PAR signaling in Huntington and neurodegenerative diseases.Journal of Huntington's disease · 2025Review
- A human Staufen1 BAC transgenic mouse exhibits abnormal autophagy and neurodegeneration across the central nervous system.Research square · 2025Article
- Transient Poly(ADP-Ribose) Triggers FUS Condensation Hysteresis via a Prion-Like Mechanism.bioRxiv : the preprint server for biology · 2025Article
- Amyotrophic lateral sclerosis caused by TARDBP mutations: from genetics to TDP-43 proteinopathy.The Lancet. Neurology · 2025Review
- Unlocking Disease-Modifying Treatments for TDP-43-Mediated Neurodegeneration.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- PARPs and ADP-ribosylation-mediated biomolecular condensates: determinants, dynamics, and disease implications.Trends in biochemical sciences · 2025Review
- Adenosine diphosphate-ribosylation greatly affects proteins function: a focus on neurodegenerative diseases.Frontiers in aging neuroscience · 2025Review
- Proteins Associated with Neurodegenerative Diseases: Link to DNA Repair.Biomedicines · 2024Review
- Membraneless organelles in health and disease: exploring the molecular basis, physiological roles and pathological implications.Signal transduction and targeted therapy · 2024Review
- Parthanatos: Mechanisms, modulation, and therapeutic prospects in neurodegenerative disease and stroke.Biochemical pharmacology · 2024Review
- Poly ADP-ribose signaling is dysregulated in Huntington disease.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating and fatal motor neuron disease. Diagnosis typically occurs in the fifth decade of life and the disease progresses rapidly leading to death within ~ 2-5 years of symptomatic onset. There is no cure, and the few available treatments offer only a modest extension in patient survival. A protein central to ALS is the nuclear RNA/DNA-binding protein, TDP-43. In > 95% of ALS patients, TDP-43 is cleared from the nucleus and forms phosphorylated protein aggregates in the cytoplasm of affected neurons and glia. We recently defined that poly(ADP-ribose) (PAR) activity regulates TDP-43-associated toxicity. PAR is a posttranslational modification that is attached to target proteins by PAR polymerases (PARPs). PARP-1 and PARP-2 are the major enzymes that are active in the nucleus. Here, we uncovered that the motor neurons of the ALS spinal cord were associated with elevated nuclear PAR, suggesting elevated PARP activity. Veliparib, a small-molecule inhibitor of nuclear PARP-1/2, mitigated the formation of cytoplasmic TDP-43 aggregates in mammalian cells. In primary spinal-cord cultures from rat, Veliparib also inhibited TDP-43-associated neuronal death. These studies uncover that PAR activity is misregulated in the ALS spinal cord, and a small-molecular inhibitor of PARP-1/2 activity may have therapeutic potential in the treatment of ALS and related disorders associated with abnormal TDP-43 homeostasis.
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