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15-Lipoxygenase inhibitor program:

Acurex Coauthored Papers

  1. Keeney, M. T., Rocha, E. M., Hoffman, E. K., Farmer, K., Di Maio, R., Weir, J., Wagner, W. G., Hu, X., Clark, C. L., Castro, S. L., Scheirer, A., Fazzari, M., De Miranda, B. R., Pintchovski, S. A., Shrader, W. D., Pagano, P. J., Hastings, T. G., & Greenamyre, J. T. LRRK2 regulates production of reactive oxygen species in cell and animal models of Parkinson’s disease. Science Translational Medicine, 16: eadl3438 (2024). https://doi.org/10.1126/scitranslmed.adl3438
  2. Keeney, M. T., Hoffman, E. K., Weir, J., Wagner, W. G., Rocha, E. M., Castro, S., Farmer, K., Fazzari, M., Di Maio, R., Konradi, A., Hastings, T. G., Pintchovski, S. A., Shrader, W. D., & Greenamyre, J. T. 15-Lipoxygenase-Mediated Lipid Peroxidation Regulates LRRK2 Kinase Activity. BioRxiv (2024). https://doi.org/10.1101/2024.06.12.598654
  3. Mahoney-Sánchez, L., Lucas-Clarke, H., Penverne, A., Evans, J. R., D’Sa, K., Strohbuecker, S., Lopez Garcia, P., Cosker, K., Soltic, D., O’Callaghan, B., Griffiths, A., Pintchovski, S. A., Plun-Favreau, H., Hallqvist, J., Mills, K., & Gandhi, S. The SNCA A53T mutation sensitizes human neurons and microglia to ferroptosis. BioRxiv (2025). https://doi.org/10.1101/2025.10.13.682089

General references

  1. Mamais, A., Batchelor, R.D. Jr, et al. Parkinson’s disease LRRK2 mutations dysregulate iron homeostasis and promote oxidative stress and ferroptosis in human neurons and astrocytes. BioRxiv (2025). https://doi.org/10.1101/2025.09.26.678370 
  2. Kong, D., Li, C., et al. Identifying genetic targets in clinical subtypes of Parkinson’s disease for optimizing pharmacological treatment strategies. Signal Transduction and Targeted Therapy, 9: 320 (2024). https://doi.org/10.1038/s41392-024-02020-x       
  3. Lin, X., Pan, M., et al. Membrane phospholipid peroxidation promotes loss of dopaminergic neurons in psychological stress-induced Parkinson’s disease susceptibility. Aging Cell, 22: e13970 (2023). https://doi.org/10.1111/acel.13970
  4. Wenzel, Sally E. et al. PEBP1 Wardens Ferroptosis by Enabling Lipoxygenase Generation of Lipid Death Signals. Cell, 171: 628 - 641 (2017). https://www.cell.com
  5. Jiang, Y.-N., Guo, Y.-Z., et al.  Tianma Gouteng granules decreases the susceptibility of Parkinson’s disease by inhibiting ALOX15-mediated lipid peroxidation. Journal of Ethnopharmacology, 256: 112824 (2020). https://doi.org/10.1016/j.jep.2020.112824
  6. Chen, Y., Fang, ZM., Yi, X. et al. The interaction between ferroptosis and inflammatory signaling pathways. Cell Death Dis 14, 205 (2023). https://doi.org/10.1038/s41419-023-05716-0
  7. Liddell, J. R., Hilton, J. B. W., et al.  Microglial ferroptotic stress causes non-cell autonomous neuronal death. Molecular Neurodegeneration, 19: 1–21 (2024). https://doi.org/10.1186/s13024-023-00691-8
  8. Ryan, S.K., Zelic, M., Han, Y. et al. Microglia ferroptosis is regulated by SEC24B and contributes to neurodegeneration. Nat Neurosci 26: 12–26 (2023). https://doi.org/10.1038/s41593-022-01221-3
  9. Minnella, A., McCusker, K. P., et al. Targeting ferroptosis with the lipoxygenase inhibitor PTC-041 as a therapeutic strategy for the treatment of Parkinson’s disease. PLOS ONE, 19: e0309893 (2024).  https://doi.org/10.1371/journal.pone.0309893
  10. Bouchaoui, H., Mahoney-Sanchez, L., et al. ACSL4 and the lipoxygenases 15/15B are pivotal for ferroptosis induced by iron and PUFA dyshomeostasis in dopaminergic neurons. Free Radical Biology & Medicine, 195: 145–157 (2022). https://doi.org/10.1016/j.freeradbiomed.2022.12.086
  11. Manivarma, T., Kapralov, A. A., et al. Membrane regulation of 15LOX-1/PEBP1 complex prompts the generation of ferroptotic signals, oxygenated PEs. Free Radical Biology & Medicine, 208: 458–467 (2023). https://doi.org/10.1016/j.freeradbiomed.2023.09.001
  12. Tu, R., Han, Z., Zhang, H., et al. From pathogenesis to treatment: the emerging role of ferroptosis in Parkinson’s disease. Frontiers in Immunology, 16: 1709561 (2025). https://doi.org/10.3389/fimmu.2025.1709561
  13. Gao, S., Zhou, L., et al. Cepharanthine Attenuates Early Brain Injury after Subarachnoid Hemorrhage in Mice via Inhibiting 15-Lipoxygenase-1-Mediated Microglia and Endothelial Cell Ferroptosis. Oxidative Medicine and Cellular Longevity, (2022). https://doi.org/10.1155/2022/4295208
  14. Feng, Z., Li, F., et al. ALOX15-Mediated Neuron Ferroptosis Was Involved in Diabetic Peripheral Neuropathic Pain. CNS Neuroscience & Therapeutics, 31: e70440 (2025). https://doi.org/10.1111/cns.70440 

T-type calcium channel antagonist program:

  1. Matthews, L. G., Puryear, C. B., et al. T-type calcium channels as therapeutic targets in essential tremor and Parkinson’s disease. Annals of Clinical and Translational Neurology, 10: 462–483 (2023). https://doi.org/10.1002/acn3.51735 
  2. Handforth, A., Homanics, G. E., et al. T-type calcium channel antagonists suppress tremor in two mouse models of essential tremor. Neuropharmacology, 59: 380–387 (2010). https://doi.org/10.1016/j.neuropharm.2010.05.012 
  3. Miwa, H., & Kondo, T. T-type calcium channel as a new therapeutic target for tremor. Cerebellum (London, England), 10: 563–569 (2011). https://doi.org/10.1007/s12311-011-0277-y 
  4. Scott, L., Puryear, C. B., et al. Translational Pharmacology of PRAX-944, a Novel T-Type Calcium Channel Blocker in Development for the Treatment of Essential Tremor. Movement Disorders, 37: 1193–1201 (2022). https://doi.org/10.1002/mds.28969 
  5. Miwa, H., Koh, J., Kajimoto, Y., & Kondo, T. Effects of T-type calcium channel blockers on a parkinsonian tremor model in rats. Pharmacology Biochemistry and Behavior, 97: 656–659 (2011). https://doi.org/10.1016/j.pbb.2010.11.014
  6. Xiang, Z., Thompson, A. D., et al. The Discovery and Characterization of ML218: A Novel, Centrally Active T-Type Calcium Channel Inhibitor with Robust Effects in STN Neurons and in a Rodent Model of Parkinson’s Disease. ACS Chemical Neuroscience, 2: 730–742 (2011). https://doi.org/10.1021/cn200090z

CaV3.2 selective calcium channel antagonist program:

  1. Tabata, Y., Imaizumi, Y., et al. T-type Calcium Channels Determine the Vulnerability of Dopaminergic Neurons to Mitochondrial Stress in Familial Parkinson Disease. Stem Cell Reports, 11: 1171–1184 (2018). https://doi.org/10.1016/j.stemcr.2018.09.006
  2. Leandrou, E., Chalata, I., et al. α-Synuclein oligomers potentiate neuroinflammatory NF-κB activity and induce CaV3.2 calcium signaling in astrocytes. Translational Neurodegeneration, 13: 11 (2024). https://doi.org/10.1186/s40035-024-00401-4 
  3. Kamau, P. M., Li, H., et al. Potent CaV3.2 channel inhibitors exert analgesic effects in acute and chronic pain models. Biomedicine & Pharmacotherapy, 153: 113310 (2022). https://doi.org/10.1016/j.biopha.2022.113310  
  4. Bourinet, E., Alloui, A., et al. Silencing of the CaV3.2 T-type calcium channel gene in sensory neurons demonstrates its major role in nociception. EMBO Journal, 24: 315–324 (2005). https://doi.org/10.1038/sj.emboj.7600515
  5. Cai, S., Gomez, K., Moutal, A., & Khanna, R. Targeting T-type/CaV3.2 channels for chronic pain. Translational Research : Journal of Laboratory and Clinical Medicine, 234: 20–30 (2021). https://doi.org/10.1016/j.trsl.2021.01.002