Grant: Operating Grant - Priority Announcement: ALS Canada Research Fund

Neuroinflammation is a hallmark of almost all neuronal pathologies, and is prominent during early stages of disease progression. However, it is unclear if the inflammation is part of the disease process or a response to the neuronal dysfunction. We recently identified the pro-inflammatory cytokine Tumor Necrosis Factor-alpha (TNF) as an endogenous regulator of glutamatergic synaptic function in the striatum, and TNF signaling at synapses could impact the development or expression of striatal dysfunctions.Our hypothesis is that TNF-mediated receptor trafficking may initially be mediating a beneficial adaptive response in the striatum to stabilize striatal function. In later stages of the diseases, the higher levels of TNF may no longer be adaptive, and may instead be contributing to excitotoxic cell damage and neurodegeneration of the striatum.