Differentiation of Stem Cells into ‘Systems of Neurotransmitter' Phenotypes Related to Alzheimer’s and Huntington’s Diseases: Application of High Throughput Peptidomic Approaches with Mass Spectrometry
Alzheimer’s disease (AD) and Huntington’s disease (HD) neurodegenerative diseases involve loss of neurons in certain brain regions. Replacement of neurons in these diseases by stem cells differentiated into functional neurotransmitter phenotypes has high potential to provide stem cell therapy for these diseases.
The nervous system utilizes integrated actions of multiple neurotransmitters that mediate communication among neurons. It is, therefore, critical to identify factors that promote differentiation of human stem cells into systems of neurotransmitters present in normal neurons. However, most studies have examined functions of only one neurotransmitter at a time, rather the groups of transmitters that function together. It is,, therefore, important to assess factors that differentiate human stem cells into profiles of neurotransmitters that represent the normal neurons. Analyses of ‘systems of neurotransmitters’ requires advanced technology in mass spectrometry for determining profiles of neurotransmitters. With the strong and long-standing efforts of the Hook laboratory to investigate peptide neurotransmitters, we have implemented state-of-the-art peptidomic technology for high throughput LC-MS/MS mass spectrometry to identify neurotransmitters. This new state-of-the-art technology will be used for this project.
Therefore, the goal of this project will be to evaluate agents that transform human stem cells into neurons containing the ‘system of neurotransmitters’ present in the normal condition of brain regions affected in AD and HD. The specific aims will (1) test growth factors and related differentiating agents to induce human stem cells into neurotransmitter phenotypes of brain regions affected in AD and HD, and (2) compare the ‘system of neurotransmitters’ in normal human hippocampus and striatum with that in differentiated stem cells to guide differentiating conditions to generate the normal ‘system of neurotransmitters’ in selected human brain regions. Such differentiated cells may provide benefit for cell therapy to improve the health of patients affected with neurodegenerative diseases.
Numerous citizens in California are affected by devastating neurodegenerative diseases, including Alzheimer’s, Huntington’s, and Parkinsons’ disease. The unique opportunity for human stem cell therapy in California provides special research that can potentially improve health for California citizens affected by these neurodegenerative diseases.
The focus of this project to utilize novel peptidomic technology to understand the systems of neurotransmitters utilized in brain function is critical to guiding research to differential human stem cells into functional brain neurons. Achievement of the goals of this project is key to providing California citizens with the hope of new medical treatments using stem cells to relieve affected patients of the detrimental neurodegeneration in brain diseases.