Hassan-Smith, Ghaniah Zeb (2015). A study of classical and novel markers of disease in multiple sclerosis. University of Birmingham. Ph.D.
|
Hassan-Smith15PhD.pdf
PDF - Accepted Version Download (10MB) |
Abstract
Multiple sclerosis (MS) is a chronic inflammatory and degenerative condition of the Central Nervous System. Focal demyelinating lesions are its neuropathological hallmark, but widespread abnormalities found in otherwise “normal-appearing” tissue are better associated with disability outcomes. HMGB1 is a promiscuous sensor of cellular stress, acting as a link between sterile damage and innate immune mechanisms, with its extra-nuclear release producing diverse outcomes.
We report novel findings of significantly increased HMGB1 expression throughout the brain tissue of MS vs. non-MS patients, particularly in macrophages/microglia and oligodendrocytes (OGD). In addition, cerebrospinal fluid HMGB1 levels were increased in early-stage MS patients compared to non-inflammatory control patients. HMGB1 stimulation in-vitro upregulates expression of its receptors in an OGD cell line, potentially propagating chronic inflammation. Expression of the Leucine Rich Repeat and Ig-domain-containing molecules, AMIGO-3 and LINGO-1 is also significantly increased by HMGB1 stimulation in-vitro. These molecules demonstrate particularly intense immunoreactivity in human brain tissue taken at biopsy, at an early disease stage. Thus, exogenous HMGB1 may influence neurodegenerative processes via AMIGO-3 and LINGO-1 and blocking their function could have therapeutic value. Increased expression of HMGB1 in OGD, however, may highlight endogenous neuroprotective mechanisms in response to an unknown trigger.
Type of Work: | Thesis (Doctorates > Ph.D.) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Award Type: | Doctorates > Ph.D. | |||||||||
Supervisor(s): |
|
|||||||||
Licence: | ||||||||||
College/Faculty: | Colleges (2008 onwards) > College of Medical & Dental Sciences | |||||||||
School or Department: | Institute of Immunology and Immunotherapy | |||||||||
Funders: | None/not applicable | |||||||||
Subjects: | R Medicine > RC Internal medicine | |||||||||
URI: | http://etheses.bham.ac.uk/id/eprint/6249 |
Actions
Request a Correction | |
View Item |
Downloads
Downloads per month over past year