Differentiation of Neural Stem Cells

Degenerative Diseases Program

Understanding age-associated complex diseases will lead to progress in treatments for dementia, Alzheimer’s or Parkinson’s disease.


Our research is focused on the role and degradation of functional vs. nonfunctional protein. It appears that inappropriate 3-dimensional protein folding is a hallmark of degenerative diseases and deteriorates with environmental changes and age. Defective protein folding is increasingly thought to be associated with many diseases ranging from cancer to metabolic and inflammatory response syndromes.

Our focus— what questions are we asking?

Our research is focused to understand how the cell discriminates functional from nonfunctional proteins to target the latter for degradation. The answers to these questions will lead to novel therapeutics for many diseases associated with aging. We study intrinsic cellular mechanisms that recognize misfolded/damaged proteins and target their degradation. Importantly, our findings have demonstrated the damaging impact of oxidative/nitrositative stress on protein structure and function in disease pathogenesis, for example the neurodegenerative diseases of Alzheimer’s and Parkinson’s, and their impact on neural synaptic structure and signaling. Finally, defective protein folding and/or degradation are now implicated in many diseases ranging from cancer to metabolic and inflammatory response syndromes.

How will our research help patients?

Scientists in this program paved the way for development of a drug for Alzheimer’s disease that, for the first time, prevents brain cell death rather than merely masking symptoms caused by the loss of these cells. A number of other strategies are now being developed that target protein folding/degradation pathways for preserving cell function in the brain and other vital organs.



Oubaha M, Miloudi K, Dejda A, Guber V, Mawambo G, Germain MA, Bourdel G, Popovic N, Rezende FA, Kaufman RJ, Mallette FA, Sapieha P
Sci Transl Med 2016 Oct 26;8(362):362ra144
Huang TY, Zhao Y, Li X, Wang X, Tseng IC, Thompson R, Tu S, Willnow TE, Zhang YW, Xu H
J Neurosci 2016 Jul 27;36(30):7996-8011
Wang C, Niu M, Zhou Z, Zheng X, Zhang L, Tian Y, Yu X, Bu G, Xu H, Ma Q, Zhang YW
Neurobiol Aging 2016 Oct;46:22-31