James W Simpkins, PhD
PO Box 9229
108 Biomedical Road
Morgantown, WV 26506
- We assess the role of mitochondria in stroke propensity and stroke damage. These studies are aims at identifying the mechanism by which mitochondrial dysfunction contributes to stroke damage and the possibility of targeting drugs to these mitochondrial defects as a therapy for prevention/acute treatment of stroke.
- Assessment of vaious classes of drugs on neuroprotection in stroke and AD. We have a drug discovery program that attempts to discover novel compounds with efficacy in stroke and AD. One such class of compounds we have termed non-feminizing estrogens.
Structure and stroke protective effects of a non-feminizing estrogen (ZYC3)
- We assess the effects of beta amyloid on mitochondrial function to determine how this neurotoxic peptide causes loss of synapses and neurons in the brain.
Short-term treatment with beta amyloid (Abeta) causes a profound decline in mitochondrial function in promary neuronal cultures.
- Saumyendra N. Sarkar, Ashley E. Russell, Elizabeth B. Engler-Chiurazzi, Keyana N. Porter, and James W. Simpkins (2018). MicroRNAs and the Genetic Nexus of Brain Aging, Neuroinflammation, Neurodegeneration, and Brain Trauma. Aging and Disease 9(6). ISSN: 2152-5250
- Shao-Hua Yang , Wenjun Li , Nathalie Sumien , Michael Forster , James W. Simpkins, Ran Liu. Alternative mitochondrial electron transfer for the treatment of neurodegenerative diseases and cancers: Methylene blue connects the dots, Progress in Neurobiology 157: 273-291, 2017.
- E.B. Engler-Chiurazzi , C.M. Brown, J.M. Povroznik , J.W. Simpkins, Estrogens as neuroprotectants: Estrogenic actions in the context of cognitive aging and brain injury, Progress in Neurobiology 157: 188-211, 2017.
- Elizabeth B. Engler-Chiurazzi, Douglas F. Covey, and James W. Simpkins, A Novel Mechanism of Non-feminizing Estrogens in Neuroprotection, Experimental Gerontology, 94:99-102.
- Russell, AE, DN Doll, SN Sarkar and JW Simpkins, TNF-α and Beyond: Rapid Mitochondrial dysfunction mediates TNF-α-induced neurotoxicity, Journal of Clinical and Cellular Immunology, 2016, 7:6 DOI: 10.4172/2155-9899.1000467
- S. Sarkar, S. Jun, S. Rellick, D.D. Quintana, J.Z. Cavendish, and J. W. Simpkins, Expression of MicroRNA-34a in Alzheimer’s Disease Brain Targets Genes Linked to Synaptic Plasticity, Energy Metabolism, and Resting State Network Activity, Brain Res. 1646: 139-151, 2016 PMID: 27235866
- Randy Strong, Richard A. Miller, Adam Antebi, Clinton M. Astle, Molly Bogue, Martin Denzel, Elizabeth Fernandez, Kevin Flurkey, Karyn L. Hamilton, Dudley W. Lamming, Martin A. Javors, João Pedro de Magalhães, Joe M. McCord, Benjamin F. Miller, Michael Müller, James F. Nelson, Juliet Ndukum, G. Ed. Rainger, Arlan Richardson, David M. Sabatini, Adam Salmon, James W. Simpkins, Nancy L. Nadon, David E. Harrison, Longer lifespan in male mice treated with a non-feminizing steroid, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer, Aging Cell. 2016 Jun 16. doi: 10.1111/acel.12496. [Epub ahead of print] PMID: 27312235
- Sarkar, S, S Jun, S, Rellick, S, and Simpkins, JW, Increased expression of miR-34a in late-onset Alzheimer’s disease (LOAD) brain mechanistically links synaptic plasticity and energy metabolism dysfunction, Brain Res. 1646: 139-151, 2016 PMID: 27235866
- Doll DM, Rellick SL, Barr TL, Ren X, Simpkins JW. Rapid mitochondrial dysfunction mediates TNF-alpha induced neurotoxicity, J Neurochem. 2015;132(4):443-451. PMID:25492727
- Doll DN, Hu H, Sun J, Lewis SE, Rellick SL, Simpkins JW, Ren X. Mitochondrial crisis in cerebrovascular endothelial cells opens the blood-brain barrier. Stroke 46:1681-1689, 2015. PMID: 25922503
- Sarkar S, Huang RQ, Logan SM, Dillon GH, Simpkins JW. Estrogens directly potentiate neuronal L-type Ca2 channels. Proc Natl Acad Sci USA. 2008;105(39):15148-15153. PMCID: PMC2575342.
- Prokai L, Prokai-Tatrai K, Perjesi P, Zharikova A, Perez E, Liu R, Simpkins JW. Quinol-based cyclic antioxidant mechanism in estrogen neuroprotection. Proc Natl Acad Sci USA. 2003;100(20):11741—11746. PMCID: PMC208828.
- Wen Y, Li W, Poteet EC, Xie L, Tan C, Yan LJ, Ju X, Liu R, Qian H, Marvin MA, Goldberg MS, She H, Mao Z, Simpkins JW, Yang SH. Alternative mitochondrial electron transfer as a novel strategy for neuroprotection. J Biol Chem. 2001;286(18):16504-16515. PMCID: PMC3091255
- Bodor N, Prokai L, Wu WM, Farag H, Joanalagadda S, Kawamura M, Simpkins JW. A strategy for delivering peptides into the central nervous system by sequential metabolism. Science. 1992; 257(5077):1698-1700. PMID: 1529356
- Bodor N, Simpkins JW. Redox delivery system for brain-specific, sustained release of dopamine. Science. 1983; 221(4605):65‑67. PMID: 6857264