• Parkinson’s disease • Neurotoxicology • Neuropharmacology • Prion diseases • Translational research • Neuroinflammation

Dr. Kanthasamy’s research on the cellular and molecular mechanisms of Parkinson’s disease and other neurodegenerative disorders has established him as a leading neuroscientist and has brought international distinction to Iowa State University. His studies focus on environmental, chemically induced neurodegenerative processes capable of producing Parkinson’s disease, and the development of novel therapeutic agents to treat neurodegenerative diseases. He has made several fundamental advances in signal transduction mechanisms associated with cell death processes in Parkinson’s disease. Dr. Kanthasamy has applied contributions that have resulted in two patents and the establishment of a new business in the ISU Research Park to promote translational drug discovery research.

1. Anantharam, V., Kitazawa, M., Wagner, J.W. Kaul, S and Kanthasamy, A.G. (2002), Caspase-3-dependent proteolytic cleavage of Protein Kinase Cdelta is essential for oxidative stress-mediated dopaminergic cell death following exposure to Methylcyclopentadienyl Manganese Tricarbonyl (MMT)., J. Neurosci., 22: 1738-1751.

2. Kitazawa, M., Wagner, J.W., Kirby, M., Anantharam, V., and Kanthasamy, A.G., (2002), Oxidative stress and mitochondrial-mediated apoptosis in dopaminergic cells exposed to Methylcyclopentadienyl Manganese Tricarbonyl, J. Pharmacol. Expt. Therapeutics, 302:26-35.

3. Kanthasamy, A.G., Kitazawa, M., Kanthasamy, A. Anantharam, V., (2003), Role of proteolytic activation of protein kinase C delta (PKCd) in oxidative stress-induced apoptosis, Antioxidants and Redox Signaling, 5: 609-619.

4. Kitazawa, M., Anantharam, V. and Kanthasamy, A.G. (2003), Dieldrin induces apoptosis by promoting caspase-3-dependent proteolytic activation of Protein Kinase Cdelta in dopaminergic cells: Relevance to oxidative stress and dopaminergic degeneration. Neuroscience, 119: 945-964.

5. Kitazawa, M., Anantharam, V. Kanthasamy, A. and Kanthasamy, A.G. (2004), Dieldrin promotes proteolytic cleavage of poly(ADP-ribose)polymerase and apoptosis in dopaminergic cells: protective effect of mitochondrial anti-apoptotic protein Bcl-2. Neurotoxicology, 25:589-98.

6. Kaul, S. Kanthasamy, A. Kitazawa, M., Anantharam, V. and Kanthasamy, A.G. (2003), Caspase-3-dependent proteolytic activation of Protein Kinase Cdelta mediates and regulates MPP+ induced apoptosis in dopaminergic cells: Relevance to oxidative stress and Parkinson’s disease. Eur. J. Neurosci., 18: 1387-1407.

7. Yang, Y., Anantharam, V. and Kanthasamy, A.G. (2004), Suppression of caspase-3 dependent proteolytic activation of protein kinase Cdelta by small interfering RNA (siRNA) attenuates MPP+-induced dopaminergic degeneration. Molecular Cellular Neuroscience, 25:406-421.

8. Kitazawa, M., Anantharam, V., Yang. Y., Hirata, Y., Kanthasamy, A and Kanthasamy, AG. (2005) Activation of protein kinase Cdelta by proteolytic cleavage contributes to manganese-induced apoptosis in dopaminergic cells: protective role of Bcl-2. Biochemical Pharmacol. 69:133-46.

9. Latchoumycandane, C., Anantharam, V., Kitazawa, M., Yang, Y., Kanthasamy, A. and Kanthasamy, AG. (2005) Protein Kinase C Delta (PKCd) is a Key Downstream Mediator of Manganese-induced Apoptosis in Dopaminergic Clonal Cells. J. Pharmacol. Expt. Therapeutics. 313:46-55.

10. Kanthasamy, AG., Kitazawa, M., Kanthasamy, A and Anantharam, V. (2005). Dieldrin-Induced Neurotoxicity: Relevance to Parkinson's Disease Pathogenesis. Neurotoxicology, 26, 701-19.

11. Kaul, S, Anantharam, V, Kanthasamy, A and Kanthasamy, AG (2005) Wild-type alpha-synuclein interacts with pro-apoptotic proteins PKCd and BAD to protect dopaminergic neuronal cells against MPP+-induced apoptotic cell death. Molecular Brain Research 139:137-52.

12. Sun, F., Anantharam, V., Latchoumycandane, C., Kitazawa, M., Yang, Y., Kanthasamy, A. and Kanthasamy, AG. (2005) Dieldrin Induces Ubiquitin-Proteasome Dysfunction in α-Synuclein Overexpressing Dopaminergic Neuronal Cells and Enhances Susceptibility to Apoptotic Cell Death. J. Pharmacol. Expt. Therapeutics 315:69-79.

13. Kaul, S, Anantharam, V, Yang, Y, Choi, C, Kanthasamy, A and Kanthasamy, AG (2005) Tyrosine Phosphorylation Regulates the Proteolytic Activation of PKCdelta In Dopaminergic Neuronal Cells. J. Biol. Chem. 280: 28721-30.

14. Sun, F., Anantharam, V., Zhang, V., Latchoumycandane, C., Kanthasamy, A. and Kanthasamy, AG. (2006) Proteasome inhibitor MG-132 induces dopaminergic degeneration in cell culture and animal models. Neurotoxicology, 27: 807-815.

15. Kanthasamy, AG, Anantharam, V., Zhang, D. Latchoumycandane, C., Jin, H., Kaul, S. and Kanthasamy, A. (2006), A novel peptide inhibitor targeted to caspase-3 cleavage site of a proapoptotic kinase protein kinase C delta (PKCd) protects against dopaminergic neuronal degeneration in Parkinson’s disease models. Free Radical Biol. Med., 41: 1578-1589.

16. Choi, C.J., Anantharam, V., Saetveit, N.J., Houk, R.S., Kanthasamy, A., Kanthasamy AG. (2007), Normal cellular prion protein protects against manganese-induced oxidative stress and apoptotic cell death. Toxicol. Sci., 98: 495-509.

17. Choi, C.J., Kanthasamy, A., Anantharam, V., Kanthasamy, A.G. (2006), Interaction of metals with prion protein: possible role of divalent cations in the pathogenesis of prion diseases. Neurotoxicol., 27: 777-87.

18. Sun, F., Kanthasamy, V. Anantharam and AG. Kanthasamy. (2007) Environmental neurotoxic chemicals-Induced ubiquitin proteasome dysfunction in the pathogenesis and progression of Parkinson’s Disease. Pharmacol and Ther., 114: 327-344.

19. Zhang, A. Kanthasamy, Y. Yang, V. Anantharam and AG. Kanthasamy. (2007). Protein kinase Cdelta negatively regulates tyrosine hydroxylase activity and dopamine synthesis by enhancing protein phosphatase-2A activity in dopaminergic neurons. J. Neurosci., 27: 5349-5362.

20. Zhang, A. Kanthasamy, Y. Yang, V. Anantharam and AG. Kanthasamy. (2007), Neuroprotective effect of PKCdelta inhibitor rottlerin in cell culture and animal models of Parkinson's Disease, J. Pharmacol. Expt. Therapeutics, 322:913-922.

21. V. Anantharam, E. Lehrmann, A. Kanthasamy, Y. Yang, P. Banerjee, KG. Becker, WJ Freed, AG. Kanthasamy (2007). Microarray Analysis of Oxidative Stress Regulated Genes in Mesencephalic Dopaminergic Neuronal Cells: Relevance to Oxidative Damage in Parkinson ’s disease. Neurochem. Intl. 50(6):834-47.

22. Anantharam V, Kanthasamy A, Choi CJ, Martin DP, Latchoumycandane C, Richt JA, Kanthasamy AG. Opposing roles of prion protein in oxidative stress- and ER stress-induced apoptotic signaling. Free Radic Biol Med. 2008; 45: 1530-41.

23. Sun, F, Kanthasamy A, Song C, Yang Y, Anantharam V, Kanthasamy AG. (2008). Proteasome inhibitor-induced apoptosis is mediated by positive feed-back amplification of PKCdelta proteolytic activation and mitochondrial translocation. J Cell Mol Med. 12,2467-2481

• Chair, Interdepartmental Toxicology Graduate Program, Iowa State University, 2003- present • Director, Parkinson’s Disorder Research Program, Dept. of Biomedical Sciences, Iowa State University, 1999- present • Founding Director, Iowa Center for Advanced Neurotoxicology (ICAN). • Member, CSR-NIH Study Section, Neurotoxicology and Alcohol (NAL), 2004-2008. • Member, CSR-NIH Study Section, Brain Disorders and Clinical Neuroscience, 1998-2003. • Research Advisory Council Member, College of Veterinary Medicine, Iowa State University, 2000-2003 • Chair, 2nd and 3rd International Conferences on Antioxidants & Free Radicals in Health and Disease, Vancouver, B.C. • Chair, International Symposium on Environmental Links to Neurodegenerative Discorders, 24th International Neurotoxicolgy Meeting, San Antonio, Texas • Chair, International Symposium on Advanced Neuroscience, Symposium on Molecular Mechanisms of Neurodegeneration, Lucknow, India, 2007 • Search Committees: 2008- Vice President for Research Economic Development, 2008-2009: Chair of Veterinary Microbiology and Preventive Medicine, Chair of Veterinary Clinical Sciences, Faculty member searches in Biomedical Sciences, Animal Science, Food and Human Nutrition, VMPM. • Consulting/counseling with many Iowa farmers and others with Parkinson's disease. 2001-present.

October 2007: Named W. Eugene and Linda R. Lloyd Endowed Chair in Neurotoxicology, ISU. Dec 2004 -2008: Member, NIH Study Section, Neurotoxicology and Alcohol (NAL) Panel. 2004, 2006, 2007, 2008: Ad hoc reviewer, NIH Study Section, Clinical Neuroscience and Disease (CND) and Clinical Neuroimmunology and Brain Tumors (CNBT); NIH Study Section, Cell Death and Injury in Neurodegeneration (CDIN, formerly BDCN-3). 1998-2003: Member, NIH- Study Section, Brain Disorder and Clinical Neurosciences-1 (BDCN-1) May 2004: Awarded the Pfizer Animal Health Award for Research, CVM, ISU. Sept. 2001: Reviewer, Michael J. Fox Foundation- NINDS grant review panel, RFA-NS-02-006, Fast Track Grants for Parkinson’s Disease Research. March 2000: Ad hoc member, NIH-NIEHS, Study Section, RFA ES 00-002 Environmental Factors in Parkinson’ Disease 1998: Reviewer, NIH-CSR, SBIR/STTR Review Panel. 1998-2001: Chair, 2nd and 3rd International Conferences on Antioxidants & Free Radicals in Health and Disease, Vancouver, B.C. 1998, 2003: Member, Grant Review Panel, Alzheimer’s Disease Association.