ArticleHuman molecular genetics2015
A novel manganese-dependent ATM-p53 signaling pathway is selectively impaired in patient-based neuroprogenitor and murine striatal models of Huntington's disease.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 69 citations in OpenAlex.
- Mapping and rewiring thebioRxiv : the preprint server for biology · 2026Article
- An In Vivo and In Silico Experimental Approach on Rats' Neurobehaviour upon Treatment with Atrazine and Manganese.Molecular neurobiology · 2025Article
- Homeostasis and metabolism of iron and other metal ions in neurodegenerative diseases.Signal transduction and targeted therapy · 2025Review
- Mechanisms and Applications of Manganese-Based Nanomaterials in Tumor Diagnosis and Therapy.Biomaterials research · 2025Review
- Manganese mediates antiviral effects by driving an ATM -TBK1 phosphorylation signaling pathway.Frontiers in immunology · 2025Article
- An Unbiased Screen Identified the Hsp70-BAG3 Complex as a Regulator of Myosin-Binding Protein C3.JACC. Basic to translational science · 2023Article
- IGF/mTORC1/S6 Signaling Is Potentiated and Prolonged by Acute Loading of Subtoxicological Manganese Ion.Biomolecules · 2023Article
- Manganese Mediates Its Antiviral Functions in a cGAS-STING Pathway Independent Manner.Viruses · 2023Article
- Carrier-free nanoprodrug for p53-mutated tumor therapy via concurrent delivery of zinc-manganese dual ions and ROS.Bioactive materials · 2023Article
- Manganese enhances DNA- or RNA-mediated innate immune response by inducing phosphorylation of TANK-binding kinase 1.iScience · 2022Article
- BTBD9 attenuates manganese-induced oxidative stress and neurotoxicity by regulating insulin growth factor signaling pathway.Human molecular genetics · 2022Article
- Exposing the role of metals in neurological disorders: a focus on manganese.Trends in molecular medicine · 2022Review
- Acclimation to Nutritional Immunity and Metal Intoxication Requires Zinc, Manganese, and Copper Homeostasis in the PathogenicFrontiers in cellular and infection microbiology · 2022Review
- YAC128 mouse model of Huntington disease is protected against subtle chronic manganese (Mn)-induced behavioral and neuropathological changes.Neurotoxicology · 2021Article
- The Phosphorylated Form of the Histone H2AX (γH2AX) in the Brain from Embryonic Life to Old Age.Molecules (Basel, Switzerland) · 2021Review
- A bistable, multiport valve enables microformulators creating microclinical analyzers that reveal aberrant glutamate metabolism in astrocytes derived from a tuberous sclerosis patient.Sensors and actuators. B, Chemical · 2021Article
- Review
- Review
- Evaluating the risk of manganese-induced neurotoxicity of parenteral nutrition: review of the current literature.Expert opinion on drug metabolism & toxicology · 2021Review
- Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update.International journal of molecular sciences · 2021Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The essential micronutrient manganese is enriched in brain, especially in the basal ganglia. We sought to identify neuronal signaling pathways responsive to neurologically relevant manganese levels, as previous data suggested that alterations in striatal manganese handling occur in Huntington's disease (HD) models. We found that p53 phosphorylation at serine 15 is the most responsive cell signaling event to manganese exposure (of 18 tested) in human neuroprogenitors and a mouse striatal cell line. Manganese-dependent activation of p53 was severely diminished in HD cells. Inhibitors of ataxia telangiectasia mutated (ATM) kinase decreased manganese-dependent phosphorylation of p53. Likewise, analysis of ATM autophosphorylation and additional ATM kinase targets, H2AX and CHK2, support a role for ATM in the activation of p53 by manganese and that a defect in this process occurs in HD. Furthermore, the deficit in Mn-dependent activation of ATM kinase in HD neuroprogenitors was highly selective, as DNA damage and oxidative injury, canonical activators of ATM, did not show similar deficits. We assessed cellular manganese handling to test for correlations with the ATM-p53 pathway, and we observed reduced Mn accumulation in HD human neuroprogenitors and HD mouse striatal cells at manganese exposures associated with altered p53 activation. To determine if this phenotype contributes to the deficit in manganese-dependent ATM activation, we used pharmacological manipulation to equalize manganese levels between HD and control mouse striatal cells and rescued the ATM-p53 signaling deficit. Collectively, our data demonstrate selective alterations in manganese biology in cellular models of HD manifest in ATM-p53 signaling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.