Role of SOCS 3 in regulating oligodendroglial phenotype in health and disease

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/305519

Funding Status
Closed

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Funded Activity Summary

The response of nerve cells, known as oligodendrocytes, to an inflammatory insult dictates the severity of demyelinating diseases such as multiple sclerosis (MS). We have previously discovered that a key protein in this response is the cytokine leukaemia inhibitory factor (LIF) which, by activating the LIF receptor expressed on these cells, limits their death and reduces the clinical impact on animal models of MS. However, the therapeutic benefit of LIF is incomplete and we do not completely understand the mechanisms by which LIF exerts these effects. To maximise the treatment potential of LIF we need to understand how LIF receptor signaling is modulated in the nervous system. An important protein known to regulate the activity of LIF and of other cytokines in other organs of the body is the suppressor of cytokine signaling 3 (SOCS 3) molecule. We have recently shown that the expression of SOCS 3 is increased in an animal model of MS, indicating that it is likely to modulate the activity of LIF in this context. We plan to investigate the nature of this regulation. SOCS 3 might limit the efficacy of LIF but it could also limit the deleterious effect of unbridled LIF receptor signaling. To distinguish between these possibilities, we plan to study the impact of demyelinating disease in animals in which SOCS 3 is either deleted or overexpressed in oligodendrocytes. In this way, we should be able to learn how to optimise the therapeutic potential of LIF in MS and related nervous system diseases.

Funded Activity Details

Start Date: 01-01-2004

End Date: 01-01-2006

Funding Scheme: NHMRC Project Grants

Funding Amount: $419,187.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Neurology and Neuromuscular Diseases

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

cytokine signaling | demyelination | multiple sclerosis | nervous system disorders | nervous system repair | oligodendrocyte

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