Alzheimer’s Disease (AD) is a neurodegenerative disorder that affects a growing population and poses a significant public health challenge. It is characterized by cognitive decline and memory loss, of which current therapies only manage symptoms or slow disease progression and does not treat the underlying disease progression. Therefore, there is an unmet need to advance the understanding of neurodegenerative disease progression, which could enable the development of novel therapies for these diseases. Emerging evidence increasingly suggests that chronic neuroinflammation in the central nervous system (CNS) is associated with neuronal injury and contributes to the onset and progression of neurodegeneration. Neuroinflammatory responses promote neurovascular impairment and exacerbates neurotoxicity.
In recent work, we have identified a key signalling pathway that converges on the transient receptor potential melastatin 2 (TRPM2) as a significant contributor to chronic pro-inflammatory activation. We initiated a small molecule drug discovery program aimed at developing a TRPM2 inhibitor to modulate neuroinflammation as a potential therapeutic strategy for the treatment of AD. The objective of this proposal is to use our lead candidate in in vivo models of neuroinflammation and bacterial infection to probe whether selective TRPM2 inhibition will resolve chronic neuroinflammation and whether it will significantly affect innate immunity.
