Durham Research Center 1, 3011
985800 Nebraska Medical Center
Omaha, NE 68198-5880
Keywords: Alzheimer's disease, Amyotrophic lateral sclerosis, Frontotemporal dementia, Multiple sclerosis, Neurodegenerative diseases, Mitochondrial dysfunction, Mitochondrial dynamics, Neuroinflammation, TDP-43 proteinopathy, Aβ, tau, Neuromuscular junction
Unmc Today | August 26, 2021
UNMC Today | April 28, 2021
Drs. Van Hook, Wang named Kinman Oldfield scholars
UNMC Today | January 04, 2021
Xinglong Wang, PhD, named inaugural Singer Professor
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 including AD, FTD and ALS.Research interests
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 neurodegeneration: Mitochondrial dysfunction has long been recognized as a prominent feature of AD, 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.Representative Publications
Gao, J., Wang, L., Ren, X., Dunn, J., Peters, A., Miyagi, M., Fujioka, H., Zhao, F., Askwith, C., Liang, J. and Wang, X. (2021) Translational regulation in the brain by TDP-43 phase separation. J. Cell Biol. 220(10): e202101019. PMID: 34427634.
Harland, M., Torres, S., Liu, J. and Wang X. (2020) Neuronal mitochondria modulation of LPS-induced neuroinflammation. J Neurosci. 40(8):1756-1765. PMID: 31937559. PMCID: PMC7046320.
Yan, T., Liang, J., Gao, J., Wang, L., Fujioka, H., ADIN, Zhu, X.F.(Xiaofeng), and Wang, X. (2020) FAM222A encodes a protein which accumulates in plaques in Alzheimer’s disease. Nat Commun. 11(1):411. Comment on: “Possible Alzheimer's breakthrough suggested” by the Daily of Case Western Reserve University; “In Alzheimer’s, New Protein Is Seen at Heart of Plaque Formation” by Genetic Engineering & Biotechnology News; “Newly Discovered Alzheimer's Gene Hints at Possible Breakthrough for the Disease” by Biospace; “Researchers Pinpoint Protein, ‘Aggregatin,’ as New Biomarker for Alzheimer’s” by Being Patient; “Case Western Researchers Identify New Gene With Potential Alzheimer's Link” by Equities; “Gene and Associated Protein May be Key to Slow Alzheimer’s Progression” by Clinical OMICs; “Novel protein suggested as core of Alzheimer’s amyloid plaques” by NEW ATLAS. PMID: 31964863. PMCID: PMC6972869.
Gao, J., Wang, L., Gao, C., Arakawa, H., Perry, G., and Wang X. (2020) TDP-43 inhibitory peptide alleviates neurodegeneration and memory loss in an APP transgenic mouse model for Alzheimer's disease. Biochim Biophys Acta Mol Basis Dis. 1866(1):165580. PMID: 31678156. PMCID: PMC6861700.
Huntley, M.L., Gao, J., Termsarasab, P., Wang, L., Zeng, S., Thammongkolchai, T., Liu, Y., Cohen, M.L., and Wang, X. (2019) Association Between TDP-43 and Mitochondria in Inclusion Body Myositis. Lab Invest. 99(7):1041-1048. PMID: 30742062. PMCID: PMC6609472.
Wang, L., Gao, J., Liu, J., Siedlak, S.L., Torres, S., Fujioka, H., Huntley, M.L., Jiang, Y., Ji, H., Yan, T., Harland, M., Termsarasab, P., Zeng, S., Jiang, Z., Liang, J., Perry, G., Hoppel, C., Zhang, C., Li, H., and Wang, X. (2018) Mitofusion 2 regulates slow axonal transport of calpastatin to prevent programed neuromuscular synaptic elimination in skeletal muscles. Cell Metab. 28(3):400-414. Preview: "Shipping Calpastatin to the Rescue: Prevention of Neuromuscular Degeneration through Mitofusin 2” in Cell Metab. 2018, 28(4):536-538. “Mitofusin2: CASTing A Line To Protect Muscles in ALS” in the ALS Research Forum. PMID: 30017354. PMCID: PMC6125186.
- Wang, W., Arakawa, H., Wang, L., Okolo, O., Siedlak, S.L., Jiang, Y., Gao, J., Xie, F., Petersen, R.B., and Wang, X. (2017) Motor coordination and cognitive dysfunction caused by mutant TDP-43 could be reversed by inhibiting its mitochondrial localization. Mol Ther. 25(1):127-139. Comment on: “New Therapeutic Avenue for ALS: Avoiding a Fatal Encounter of TDP-43 at the Mitochondria” in Mol Ther. 2017, 25(1):10-11. PMID: 28129109. PMCID: PMC5363201.
- Wang, W., Wang, L., Lu, J., Siedlak, S.L., Fujiok, H., Liang, J., Jiang, S., Ma, X., Zhen, J., Rocha, E.L., Sheng, M., Choi, H., Lerou, P.H., Li, H., and Wang, X. (2016). The Inhibition of TDP-43 Mitochondrial Localization Blocks Its Neuronal Toxicity. Nat Med. 22(8):869-878. Comment on: “Unleashed From the Nucleus, TDP-43 Wreaks Havoc in Mitochondria” in in the ALS Research Forum; “From the Bench: TDP-43 Accumulation in Mitochondria May Drive ALS/FTD Toxicity” in Neurology Today, 2016, 16(17), 42–44; “ALS Culprit Protein Chokes Mitochondria, Killing Neurons, According to Recent Discovery” in ALS NEWS TODAY; “Protein’s Misconduct in Mitochondria May Be Cause of Nerve Cell Death in Huntington’s” in the Huntington’s Disease News; “Scientists Prevent Nerve Cell Death and Neurodegenerative Disease Progression” in Kerafast; “Scientists keep a molecule from moving inside nerve cells to prevent cell death” by Case Western Reserve University School of Medicine. PMID: 27348499. PMCID: PMC4974139.
- Wang, W., Wang, X.*, Fujioka, H., Hoppel, C., Whone, A.L., Caldwell, M.A., Cullen, P.J., Liu, J.* and Zhu, X.* (2016). Parkinson's disease-associated mutant VPS35 causes mitochondrial dysfunction by recycling DLP1 complexes. Nat Med. 22(1):54-63. *corresponding author. PMID: 26618722. PMCID: PMC4826611.
- 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. 290:168-182. “Paper of the Week”. PMID: 25416777. PMCID: PMC4281719.
- 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(23):4706-4719. PMID: 23827948. PMCID: PMC3820133.
Additional publications in PubMed