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The role of inflammatory mediators S100B, HMGB1 and TWEAK in MPTP induced neurotoxicity

Parkinson’s disease is among the commonest debilitating neurodegenerative disorders. The disease is characterised by severe motor symptoms, including uncontrollable tremor, postural instability, slowness of movement and rigidity. The prominent pathological hallmark of the disease is a pronounced loss of dopamine-producing neurons in the substantia nigra (SN), which results in a drastic decrease in dopamine in the striatum, to which these neurons project. The etiology of disease progression has not yet been fully understood. A number of hypotheses have implicated environmental toxins including metals, pesticides etc and genetic factors to play a role in pathogenesis of PD. It is proposed that a cross-talk of environmental and genetic factors may also be involved. A variety of mechanisms that are believed to cause accelerated cell death have also been suggested, including oxidative stress, excitotoxicity and mitochondrial dysfunction and inflammation. Inflammatory pathways have emerged as primary players in the degenerative process seen in Parkinson’s disease. This study focuses on the role of inflammatory pathways, in particular those mediated via S100B, HMGB1 and TWEAK. S100B has been implicated in stroke, cerebral ischemia and in Alzheimer’s disease. HMGB1 a chromatin binding protein was also shown to be involved in stroke, sepsis and more recently Alzheimer’s disease. TWEAK signalling pathway is activated in tumour progression. Thus all of these proteins have been implicated in inflammation seen in a number of diseases. All these proteins have been looked at individually, but their role in neuroinflammation seen in PD is not yet completely understood. This was the main reason we selected these proteins. MPTP, a neurotoxin mimics parkinsonian conditions and has been widely used as a toxin model. In this study we assess the importance of S100B, HMGB1 and TWEAK using the MPTP mouse model of PD.

Identiferoai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:531914
Date January 2010
CreatorsSathe, Kinnari
PublisherUniversity of Aberdeen
Source SetsEthos UK
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Sourcehttp://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=158387

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