Molecular Neuroscience and Dementia Research

Dementia is a common neurological syndrome affecting physical fitness and life quality in the elderly. The prevalence of neurodegenerative diseases is expected to increase dramatically due to the aging global population. Our research focuses on dementia-associated neurodegenerative diseases, including Alzheimer's disease, frontotemporal lobe degeneration, ischemia stroke, subarachnoid hemorrhage, brain trauma…etc. Degeneration and death of neurons are the fundamental processes responsible for the clinical manifestations of neurodegenerative dementia. We are devoted to investigating the molecular mechanisms of pathogenesis in neurodegenerative diseases. Based on molecular biology and cell biology, our research combines physiological tools, neuroethological methods, and disease animal models. We are interested in the basic functions of genes/proteins in the brain and their correlations with neurodegenerative diseases. Furthermore, we are trying to develop new medical strategies (drugs, chemical compounds, and stem cell therapies) for achieving the aim of translation medicine.

1. Chu Y.P., Ho P.C., Tsai K.J.* (2023) TTR (transthyretin) leads the autophagy disaster relief team against TARDBP/TDP-43 proteinopathy. Autophagy, 19(8):2403-2405.
2. Chu Y.P., Jin L.W., Wang L.C., Ho P.C., Wei W.Y., Tsai K.J.* (2023) Transthyretin attenuates TDP-43 proteinopathy by autophagy activation via ATF4 in FTLD-TDP. Brain, 146(5):2089-2106.
3. Wang I.F., Wang Y.H., Yang Y.H., Huang G.J., Tsai K.J.*, Shen C.K.J.* (2021) Activation of a hippocampal CREB-pCREB-miRNA-MEF2 axis modulates individual variation of spatial learning and memory capability. Cell Reports, 36(5):109477.
4. Wong C.E., Jin L.W., Chu Y.P., Wei W.Y., Ho P.C., Tsai K.J.* (2021) TDP-43 proteinopathy impairs mRNP granule mediated postsynaptic translation and mRNA metabolism. Theranostics, 11(1): 331-346.
5. Wu C.C., Jin L.W., Wang I.F., Wei W.Y., Ho P.C., Liu Y.C., Tsai K.J.* (2020) HDAC1 dysregulation induces aberrant cell cycle and DNA damage in progress of TDP-43 proteinopathies. EMBO Molecular Medicine, 12(6):e10622.
6. Yoshihito H, Lin H.T., Lee C.C., Tsai K.J.* (2020) Effects of Neural stem cell transplantation in Alzheimer’s disease models. Journal of Biomedical Science​​, 27, 29.
7. Wu C.C., Wang L.C., Su Y.T., Wei W.Y., Tsai K.J.* (2018) Synthetic α5β1 Integrin Ligand PHSRN is Proangiogenic and Neuroprotective in Cerebral Ischemic Stroke. Biomaterials, 185:142-154.
8. Fang Y.S., Tsai K.J., Chang Y.J., Kao P., Woods R., Kuo P.H., Wu C.C., Liao J.Y., Chou S.C., Lin V., Jin L.W., Yuan H.S., Cheng I.H., Tu P.H., Chen Y.R.* (2014) Full-length TDP-43 forms toxic amyloid oligomers that are present in frontotemporal lobar dementia-TDP patients. Nature Communications, 5:4824.
9. Wang I.F., Tsai K.J.* and Shen C.K.* (2013) Autophagy activation ameliorates neuronal pathogenesis of FTLD-U mice: A new light for treatment of TARDBP/TDP-43 proteinopathies. Autophagy 9(2):239-240.
10. Wang H.K., Lin S.H., Sung P.S., Wu M.H., Hung K.W., Wang L.C., Huang C.Y., Lu K., Chen H.J., Tsai K.J.* (2012) Population-based study on patients with traumatic brain injury suggests increased risk of dementia. Journal of Neurology, Neurosurgery, and Psychiatry, 83(11), 1080-1085.
11. Wang I.F., Guo B.S., Liu Y.C., Wu C.C., Yang C.H., Tsai K.J.*, Shen C.K.J.* (2012) Autophagy activators rescue and alleviate pathogenesis of a mouse model with proteinopathies of the TAR DNA-binding protein 43. Proceedings of the National Academy of Science USA 109(37):15024-15029.
12. Majumder P., Chen Y.T., Bose J.K., Wu C.C., Cheng W.C., Cheng S.J., Fang Y.H., Chen Y.L., Tsai K.J., Lien C.C., Shen C.K.* (2012) TDP-43 regulates the mammalian spinogenesis through translational repression of Rac1. Acta Neuropathologica, 124(2), 231-45.
13. Tsai K.J., Yang C.H., Fang Y.H., Cho K.H., Chien W.L., Wang W.T., Wu T.W., Lin C.P., Fu W.M. and Shen C.K.J.* (2010) Elevated expression of TDP-43 in the forebrain of mice is sufficient to cause neurological and pathological phenotypes mimicking FTLD-U. Journal of Experimental Medicine 207:1661-1673.
14. Tsai K.J., Tsai Y.C. and Shen C.K.J.* (2007) G-CSF rescues the memory impairment of animal models of Alzheimer’s disease. Journal of Experimental Medicine 204:1273-1280.