Microglial restoration and systemic rejuvenation to treat age-related neurodegenerative disease
Abstract/Contents
- Abstract
- A rapidly aging population and a limited therapeutic toolbox urgently necessitate new approaches to treat neurodegenerative diseases. Brain aging involves complex cellular and molecular processes that eventually result in cognitive decline. While cell-intrinsic defects in neurons, the effector cells of behavior, memory, and consciousness, may partially explain this decline, cell-extrinsic changes in the local environment, mediated by glia, and the systemic environment, mediated by blood, have recently been shown to drive chronic inflammation and subsequent brain dysfunction with age. Here, I describe my efforts to understand systemic mediators of brain aging and rejuvenation, to restore brain-resident immune cell function, and to develop next-generation glia-directed therapies for neurodegenerative disease. In the first case, I review the current understanding of how systemic factors interact with the brain sequentially, starting with known sources of systemic factors, conduits and barriers to entry, cellular targets in the brain, and clearance mechanisms. Next, I elucidate a mechanism of age-related microglial impairment and a strategy to restore homeostasis in the aging brain. Finally, I propose a microglia-directed treatment to ameliorate cognitive decline in Alzheimer's disease. Taken together, this work illuminates the roles of systemic and local brain inflammation on age-related cognitive dysfunction and provides new microglia-directed therapeutic strategies to restore homeostasis in the aging brain and to treat neurodegenerative diseases.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Pluvinage, John Vincent |
|---|---|
| Degree supervisor | Wyss-Coray, Anton |
| Thesis advisor | Wyss-Coray, Anton |
| Thesis advisor | Bassik, Michael |
| Thesis advisor | Monje-Deisseroth, Michelle |
| Degree committee member | Bassik, Michael |
| Degree committee member | Monje-Deisseroth, Michelle |
| Associated with | Stanford University, Program in Stem Cell Biology and Regenerative Medicine. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | John Vincent Pluvinage. |
|---|---|
| Note | Submitted to the Program in Stem Cell Biology and Regenerative Medicine. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by John Vincent Pluvinage
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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