Xinglong Wang, Ph.D.

Assistant Professor

Mailing Address:
2103 Cornell Rd.
Wolstein Research Building 5122
Cleveland, OH 44106-7288

phone: (216) 368-2957
fax: (216) 368-0494


Dr. Wang received his Ph.D. in pathology from the Case Western Reserve University in 2009. Following postdoctoral training at the Department of Pathology, he was promoted to Instructor of Pathology in 2011 and has became an Assistant Professor in 2013.


Alzheimer’s disease (AD) is the most prevalent form of dementia characterized by neuronal loss in the neocortex and hippocampus. Frontotemporal dementia (FTD) is the second most common form of early-onset dementia caused by neuronal loss in the frontal and temporal cortex. Amyotrophic lateral sclerosis (ALS) is the most common motor disease characterized by progressive motor neuron degeneration in brain stem and spinal cord. My research interest is to understand the mechanism(s) underlying neuronal death in various major neurodegenerative diseases with a focus on AD, FTD and ALS.

Pathomechanisms of TDP-43 neurotoxicity
Genetic mutations in TAR DNA-binding protein 43 (TDP-43) cause ALS and FTD, and the increased presence of TDP-43 in the cytoplasm is a prominent histopathological feature of degenerating neurons in ALS, FTD and AD. One major focus of our current research is about the molecular pathomechanisms of TDP-43.

Mitochondrial dysfunction in FTD and ALS
Mitochondrial dysfunction has long been recognized as a prominent feature of FTD and ALS. However, the mechanisms responsible for the mitochondrial impairment, and its role in these diseases were not clear. Mitochondria are dynamic organelles that undergo continual fission and fusion events which serve crucial physiological function. Another focus of our research is the potential role of mitochondria dynamics in mitochondrial dysfunction and neurodegeneration in FTD and ALS.

Mitochondria in primary neurons (left) and neuronal cell lines (middle and right)



Zhang, F., Wang, W., Siedlak, S., Liu, Y., Liu, J., Jiang, K., Perry, G., Zhu, X., and Wang, X. (2015) Miro1 Deficiency in Amyotrophic Lateral Sclerosis. Frontiers in Aging Neuroscience. 7:100. doi: 10.3389/fnagi.2015.0010.

Wang, W., Zhang, F., Li, L., Tang, F, Siedlak, S. L., Liu, Y., Su, B., Fujioka, H. and Wang, X. (2015) Mfn2 Couples Glutamate Excitotoxicity and Mitochondrial Dysfunction in Motor Neurons. J Biol Chem., 290:168-82. “Paper of the Week”

Zhang, F., Su, B., Wang, C., Siedlak, S.L., Mondragon-Rodriguez, S., Lee, Hyoung-gon., Wang, X., Perry, G. and Zhu, X. (2015) Posttranslational Modifictions of α-Tubulin in Alzheimer Disease. Translational Neurodegeneratio. 4:9. doi: 10.1186/s40035-015-0030-4.


Hwang, R.D., Wiemerslage, L., LaBreck, C.J., Khan, M., Kannan, K., Wang, X., Zhu, X., Lee, D. and Fridell, Y.W. (2014) The neuroprotective effect of human uncoupling protein 2 (hUCP2) requires cAMP-dependent protein kinase in a toxin model of Parkinson's disease. Neurobiol Dis. 69C:180-91.

Li, L., Wang, W., Welford, S., Zhang, T., Wang, X. and Zhu, X. (2014) Ionizing radiation causes increased tau phosphorylation in primary neurons. J Neurochem. 131:86-93.

Wang, X., Wang, W., Li, L., Perry, G., Lee, H.G., Zhu, X. (2014) Oxidative Stress and Mitochondrial Dysfunction in Alzheimer's Disease. Biochim Biophys Acta. 8:1240-47.

Bonda, D.J., Wang, X., Lee, H.G., Smith, M.A., Perry, G. and Zhu, X. (2014) Neuronal failure in Alzheimer's disease: a view through the oxidative stress looking-glass. Neurosci Bull. 30:243-52.


Wang, W., Li, L., Lin, W., Dickson, D. W., Petrucelli, L. and Wang, X. (2013) The ALS disease associated mutant TDP-43 impairs mitochondrial dynamics and function in motor neurons. Hum Mol Genet, 22:4706-19.

Zhu, X, Perry, G, Smith, M.A., Wang, X. Abnormal Mitochondrial Dynamics in the Pathogenesis of Alzheimer's Disease. (2013) J Alzheimers Dis. 33 Suppl 1, S253-62.

Yan, M.H., Wang, X, Zhu X. Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease. (2013) Free Radic Biol Med. 62, 90-101.

Zhu, X, Perry, G, Smith, M.A., Wang, X. Abnormal Mitochondrial Dynamics in the Pathogenesis of Alzheimer's Disease. (2013) J Alzheimers Dis. 33 Suppl 1, S253-62.

Yan, M.H., Wang, X, Zhu X. Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease. (2013) Free Radic Biol Med. 62, 90-101.


Sheng, B., Wang, X., Su, B., Lee, H.G., Casadesus, G., Perry, G., Zhu, X. (2012) Impaired Mitochondrial Biogenesis Contributes to Mitochondrial Dysfunction in Alzheimer's Disease. J. Neurochem. 120(3):419-29.

Kudo, W., Lee, H.P., Zou, W.Q., Wang, X., Perry, G., Zhu, X., Smith, M.A., Petersen, R.B., Lee, H.G. (2012) Cellular Prion Protein Is Essential for Oligomeric Amyloid-β-Induced Neuronal Cell Death. Hum Mol Genet. 21(5):1138-44.

Liu, K., Guo, T.L., Chojnacki, J., Lee, H., Wang, X., Siedlak, S.L., Rao, W., Zhu, X., Zhang, S. (2012) Bivalent ligand containing curcumin and cholesterol as fluorescence probe for Aβ plaques in Alzheimer's disease. ACS Chemical Neuroscience , 3:141−146.

Wang, X*, Yan, M., Fujioka, H., Liu, J., Wilson-Delfosse, A., Chen, S., Perry, G., Casadesus, G., Zhu, X. (2012) LRRK2 Regulates Mitochondrial Dynamics and Function through Direct Interaction with DLP1. Hum Mol Genet. 21:1931-44. *co-corresponding author

Lee, H.P., Pancholi, N., Esposito, L., Previll, L.A., Wang, X., Zhu, X., Smith, M.A., Lee HG. (2012) Early induction of oxidative stress in mouse model of Alzheimer disease with reduced mitochondrial superoxide dismutase activity. PLoS One. 7:e28033.

Wang, X*, Snape, M., Klann, E., Stone, J.G., Singh, A., Petersen, R.B., Castellani, R.J., Casadesus, G. Smith, M.A., Zhu, X. (2012) Activation of the extracellular signal-regulated kinase pathway contributes to the behavioral deficit of fragile x-syndrome. J. Neurochem. 121:672-9. *co-corresponding author

Wang, X.*, Petrie, T.G., Liu, Y., Liu, J., Fujioka, H., Zhu, X. (2012) Parkinson's Disease-Associated DJ-1 Mutations Impair Mitochondrial Dynamics and Cause Mitochondrial Dysfunction. J Neurochem. 121:830-9. *co-corresponding author

Rodrigues, R., Smith, M.A., Wang, X., Perry, G., Lee, H., Zhu, X. and Petersen, R.B. (2012) Molecular neuropathogenesis of Alzheimer’s disease: an interaction model stressing the central role of oxidative stress, Future Neurology 7, 287-305.

Selected Publications Before 2012

Wang, X., Su, B., Gao, Y., Perry, G., Smith, M.A. and Zhu, X. (2011) DLP1-Dependent Mitochondrial Fragmentation Mediates 1-methyl-4-phenylpyridinium Toxicity in Neurons: Implications for Parkinson’s Disease. Aging Cell. 10(5):807-23.

Bevilacqua, E. *, Wang, X.*, Majumder, M.*, Gaccioli, F., Yuan, C.L., Zhu, X., Jordan, L.E., Scheuner, D., Kaufman, R.J., Koromilas, A.E., Snider, M.D., Holcik, M. and Hatzoglou, M. (2010) eIF2alpha Phosphorylation Tips The Balance To Apoptosis During Osmotic Stress. J Biol Chem. 285(22):17098-111. *co-first author

Wang, X., Su, B., Perry, G., Smith, M.A. and Zhu, X. (2009) The role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer's disease. J. Neurochem., 109 Suppl 1:153-159

Wang, X., Su, B., Lee, H., Li, X., Perry, G., Smith, M.A. and Zhu, X. (2009) Impaired balance of mitochondrial fission and fusion in Alzheimer’s disease. J Neurosci., 29, 9090-9103.

Wang, X., Su, B., Siedlak, S., Moreira, P.I., Fujioka, H., Wang, Y., Casadesus, G., and Zhu, X. (2008) Aβ Overproduction Causes Abnormal Mitochondrial Dynamics via Modulation of Mitochondrial Fission/Fusion Proteins. Proc Natl Acad Sci USA, 105, 19318-19323

Wang, X., Su, B., Fujioka, H. and Zhu, X. (2008) DLP1 reduction underlies mitochondrial morphology and distribution abnormalities in fibroblasts from sporadic Alzheimer disease patients. Am J Pathol., 173, 470-482.

See More Publications at:

Post-doctoral Scholar / Graduate Student Position Available:
Interested postdoctoral candidates should send their CV and contact information for three references to
Current Case Western Reserve University graduate students are also welcome to discuss potential rotation in the laboratory.