Does TNF alpha promote excitotoxic neuronal death through upregulation of calcium-permeable AMPA receptor?

Description:

What this research means to you: Excessive amounts of a chemical called glutamate, found in the central nervous system, cause damage to motor neurones in MND. This project will investigate why motor neurones are particularly vulnerable to this type of damage; if the researchers can identify the cause of this vulnerability, they may be able to highlight potential targets for future treatments.

The researcher explains in more detail: “There is now abundant evidence that glutamate toxicity plays a role in motor neurone death. Why motor neurones are particularly vulnerable to this toxicity is unknown, but it is possible that they are sensitised by factors present within the spinal cord. This grant will support a PhD student carrying out experiments to test the novel concept that a molecule named TNF a exacerbates glutamate toxicity. TNF a is made in the spinal cord and previous research has shown that it is present at higher levels in people with MND compared to the general population. It is proposed that TNF a makes motor neurones more susceptible to the damaging effects of glutamate by increasing the ability of glutamate to bind to motor neurones at specific receptor sites (the ‘calcium-permeable AMPA receptors’ mentioned in the title of this project). If this is the case, then it raises several potential drug-based therapeutic strategies to protect motor neurons.”

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