Characterising the role of AMIGO3 in oligodendrocytes and demyelinating diseases

Foale, Simon (2019). Characterising the role of AMIGO3 in oligodendrocytes and demyelinating diseases. University of Birmingham. Ph.D.

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Abstract

Demyelination disrupts neuronal signalling and can have profound effects on neurological control. No therapies currently exist to encourage remyelination and treatment options are based on preventing further demyelination highlighting the need to develop effective therapies for demyelinating diseases. Recent trials aimed at the leucine rich repeat (LRR) protein, LINGO1 to encourage remyelination have shown promising preclinical data however phase II clinical trials have been unsuccessful. The analogous LRR protein, AMIGO3 is predicted to overcome LINGO1 inhibition and therefore needs to be investigated for its role in oligodendroglia. We have investigated the expression profile of AMIGO3 in myelination and demyelinating disease. AMIGO3 is upregulated rapidly in oligodendrocyte precursor cells (OPCs) following trauma and in experimental autoimmune encephalomyelitis (EAE). Downregulation of AMIGO3 also corresponds with development myelination however AMIGO3 mRNA levels do not change following induction of OPC maturation in vitro. As AMIGO3 is raised following trauma, AMIGO3 could provide a pathological inhibition of OPC maturation in demyelinating diseases. We have also identified the NgR1 receptor complex on OPCs highlighting a potential biding partner that AMIGO3 could function through in disease. These data suggest that therapies aimed at inhibiting AMIGO3 will be promising in encouraging remyelination and treating demyelinating diseases.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):