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Novel Mechanisms of Pesticide-Induced Neurotoxicity

Description: Narrative Chronic exposure to mitochondria-impairing neurotoxic pesticides is a major public health problem around the world and has been linked to many disease conditions including Parkinson’s disease. Despite the established link, the cellular and molecular mechanisms central to the role of mitochondria-impairing pesticide exposure in the pathogenesis of Parkinson’s disease remain unidentified. This proposal will systematically characterize the mechanisms of mitochondria-inhibiting neurotoxic pesticide-induced degeneration of nigrostriatal neurons using both neuronal cell culture and animal models to discern the role of the histone acetylation pathway in chronic pesticide exposure as it relates to the etiopathogenesis of Parkinson’s disease.
Funding type: research
Funder scheme: R01
Start date: 2017-04-01
End date: 2024-03-31
Investigator: ANUMANTHA GOUNDER KANTHASAMY
Institution: UNIVERSITY OF GEORGIA
Subfield: Plant Science
Funded outputs count: 34
Funder award ID: R01ES027245
OpenAlex ID: G2390928734
Kv1.3 as an upstream regulator of oxidative stress-mediated neuroinflammation following organic dust exposure in murine in vitro, ex vivo, and in vivo models
2026 · Nyzil Massey, Sanjana Mahadev Bhat, et al. · Frontiers in Toxicology
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Pathological α-synuclein dysregulates epitranscriptomic writer METTL3 to drive neuroinflammation in microglia
2025 · Cameron Miller, Alyssa Ealy, et al. · Cell Reports · 21
Mitochondrial stress disassembles nuclear architecture through proteolytic activation of PKCδ and Lamin B1 phosphorylation in neuronal cells: implications for pathogenesis of age-related neurodegenerative diseases
2025 · Adhithiya Charli, Jie Luo, et al. · Frontiers in Cellular Neuroscience · 7
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Nuclear pore and nucleocytoplasmic transport impairment in oxidative stress-induced neurodegeneration: relevance to molecular mechanisms in Pathogenesis of Parkinson’s and other related neurodegenerative diseases
2024 · Zainab Riaz, Gabriel S. Richardson, et al. · Molecular Neurodegeneration · 19
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Manganese Exposure Enhances the Release of Misfolded α-Synuclein via Exosomes by Impairing Endosomal Trafficking and Protein Degradation Mechanisms
2024 · Dharmin Rokad, Dilshan S. Harischandra, et al. · International Journal of Molecular Sciences · 10
Mitochondrial stress-induced H4K12 hyperacetylation dysregulates transcription in Parkinson’s disease
2024 · Minhong Huang, Huajun Jin, et al. · Frontiers in Cellular Neuroscience · 8
Epitranscriptomic reader YTHDF2 regulates SEK1(MAP2K4)-JNK-cJUN inflammatory signaling in astrocytes during neurotoxic stress
2024 · Emir Malovic, Alyssa Ealy, et al. · iScience · 10
Mito-metformin protects against mitochondrial dysfunction and dopaminergic neuronal degeneration by activating upstream PKD1 signaling in cell culture and MitoPark animal models of Parkinson’s disease
2024 · Muhammet Ay, Adhithiya Charli, et al. · Frontiers in Neuroscience · 16
Environmental chemical-induced adverse effects on gut microbiota and their implications for the etiopathogenesis of chronic neurological diseases
2024 · Piyush Padhi, Gary Zenitsky, et al. · Advances in neurotoxicology · 1
Microglial immune regulation by epigenetic reprogramming through histone H3K27 acetylation in neuroinflammation
2023 · Minhong Huang, Emir Malovic, et al. · Frontiers in Immunology · 64
Impact of Environmental Risk Factors on Mitochondrial Dysfunction, Neuroinflammation, Protein Misfolding, and Oxidative Stress in the Etiopathogenesis of Parkinson’s Disease
2022 · Minhong Huang, Alejandra Bargues-Carot, et al. · International Journal of Molecular Sciences · 106
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Environmental neurotoxic pesticide exposure induces gut inflammation and enteric neuronal degeneration by impairing enteric glial mitochondrial function in pesticide models of Parkinson’s disease: Potential relevance to gut-brain axis inflammation in Parkinson’s disease pathogenesis
2022 · Bharathi N. Palanisamy, Souvarish Sarkar, et al. · The International Journal of Biochemistry & Cell Biology · 28
Mitoapocynin Attenuates Organic Dust Exposure-Induced Neuroinflammation and Sensory-Motor Deficits in a Mouse Model
2022 · Nyzil Massey, Denusha Shrestha, et al. · Frontiers in Cellular Neuroscience · 11
Mitochondrial dysfunction–induced H3K27 hyperacetylation perturbs enhancers in Parkinson’s disease
2021 · Minhong Huang, Dan Lou, et al. · JCI Insight · 41
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Chronic Manganese Exposure and the Enteric Nervous System: An in Vitro and Mouse in Vivo Study
2021 · Shivani Ghaisas, Dilshan S. Harischandra, et al. · Environmental Health Perspectives · 30
Fyn Kinase-Mediated PKCδ Y311 Phosphorylation Induces Dopaminergic Degeneration in Cell Culture and Animal Models: Implications for the Identification of a New Pharmacological Target for Parkinson’s Disease
2021 · Hariharan Saminathan, Anamitra Ghosh, et al. · Frontiers in Pharmacology · 13
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Characterization of nonmotor behavioral impairments and their neurochemical mechanisms in the MitoPark mouse model of progressive neurodegeneration in Parkinson's disease
2021 · Monica R. Langley, Shivani Ghaisas, et al. · Experimental Neurology · 32
Organic dust exposure induces stress response and mitochondrial dysfunction in monocytic cells
2021 · Sanjana Mahadev Bhat, Denusha Shrestha, et al. · Histochemistry and Cell Biology · 7
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Organic dust-induced mitochondrial dysfunction could be targeted via cGAS-STING or cytoplasmic NOX-2 inhibition using microglial cells and brain slice culture models
2021 · Nyzil Massey, Denusha Shrestha, et al. · Cell and Tissue Research · 13
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Mechanisms of organic dust induced neuroinflammation
2021 · Nyzil Massey
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Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK) Enhances Activation of STAT3/NLRC4 Inflammasome Signaling Axis through PKCδ in Astrocytes: Implications for Parkinson’s Disease
2020 · Manikandan Samidurai, Prashant Tarale, et al. · Cells · 31
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Mitochondrial Dysfunction Induces Epigenetic Dysregulation by H3K27 Hyperacetylation to Perturb Active Enhancers in Parkinson’s Disease Models
2019 · Minhong Huang, Dan Lou, et al. · bioRxiv (Cold Spring Harbor Laboratory) · 4
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MitoPark transgenic mouse model recapitulates the gastrointestinal dysfunction and gut-microbiome changes of Parkinson’s disease
2019 · Shivani Ghaisas, Monica R. Langley, et al. · NeuroToxicology · 49
Neurotoxicity of pesticides
2019 · Jason R. Richardson, Vanessa Fitsanakis, et al. · Acta Neuropathologica · 551
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Mitochondrial Impairment Upregulates MICOS Expression in a Human Microglial Cell Model
2019 · Alejandra Bargues Carot, Emir Malovic, et al. · The FASEB Journal
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