Small heat shock proteins as novel anti-inflammatory therapeutics for neurological diseases : multiple sclerosis and stroke
Abstract/Contents
- Abstract
- This thesis explores the use of small heat shock proteins as anti-inflammatory therapeutics in the context of neurological diseases, specifically multiple sclerosis (MS) and stroke. The family of small heat shock proteins (sHSPs) has been extensively studied as intracellular molecular chaperones. However, recent studies looking at the role of sHSPs in neurological diseases have demonstrated a near universal upregulation of certain sHSPs in damaged and diseased brains. Initially, it was thought that sHSPs are pathological in these disease states, but transgenic overexpression and exogenous administration of sHSPs in various experimental disease paradigms have shown just the contrary -- that sHSPs are protective, not pathological. In this thesis, I have found that members of the family of sHSPs are protective and therapeutic in mouse models of multiple sclerosis and stroke, experimental autoimmune encephalomyelitis (EAE) and middle cerebral artery occlusion (MCAO), respectively. Alpha B crystallin (cryab), a member of the sHSP family, is elevated in stroke and deficiency of cryab leads to worse disease outcome, illustrating the protective role of alpha B crystallin. Exogenous administration of small heat shock proteins, including alpha B crystallin, decreases disease severity by modulating the immune system. This leads to the conclusion that sHSPs are endogenous anti-inflammatory and neuroprotectant molecules produced after neurological disease, whose beneficial properties can be augmented when administered therapeutically.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2011 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Brownell, Sara Elaine | |
|---|---|---|
| Associated with | Stanford University, Department of Biology. | |
| Primary advisor | Steinman, Lawrence | |
| Thesis advisor | Steinman, Lawrence | |
| Thesis advisor | Robinson, William (William Hewitt) | |
| Thesis advisor | Sapolsky, Robert M | |
| Thesis advisor | Shatz, Carla J | |
| Advisor | Robinson, William (William Hewitt) | |
| Advisor | Sapolsky, Robert M | |
| Advisor | Shatz, Carla J |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Sara Elaine Brownell. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Ph.D. Stanford University 2011 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Sara Elaine Brownell
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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