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Title: A study of classical and novel markers of disease in multiple sclerosis
Author: Hassan-Smith, Ghaniah Zeb
ISNI:       0000 0004 5363 3282
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2015
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: RC Internal medicine