We are particularly interested in the relationship between tau phosphorylation, aggregation and filament formation during the development of pathology in Alzheimer's disease and related tauopathies, and are examining the impact of protein kinase inhibitors as potential therapeutic agents for the treatment of tauopathy.

Molecular mechanisms involved in the pathogenesis of Alzheimer's disease and related neurodegenerative disorders.

Our work focuses on investigating the molecular mechanisms underlying the development and progression of neurodegenerative diseases such as Alzheimer’s disease and related dementias. We use a diverse range of model systems to examine key proteins and pathways implicated in neurodegeneration and to conduct pre-clinical studies with potential therapeutics.

Main projects

1. Abnormal tau processing and altered tau function in dementias.

We have a particular interest in tau protein modifications and how these alter tau function and contribute to the development of disease. We, and our collaborators have demonstrated important roles for the tau kinases cdk5, GSK-3, c-Abl and Fyn in Alzheimer’s disease and related tauopathies. We have investigated the role of tau phosphorylation and cleavage on tau function and tau-associated neurotoxicity, and have conducted pre-clinical studies using tau protein modifiers.

2. Neuroinflammatory responses and neuron-glial interactions in Alzheimer’s disease.

Neuroinflammation is a prominent feature of Alzheimer’s disease (AD) brainthat may modulate disease progression. We have shown that minocycline, an anti-inflammatory agent, is neuroprotective in models of Alzheimer’s disease, acting to reduce astrocyte activation and suppress the release of key pro-inflammatory mediators from these glial cells. We have also found that astrocytes play a key role in mediating Aβ-induced neurotoxicity and Aβ-induced tau phosphorylation in cortical neurons. We are currently investigating novel anti-inflammatory therapies in models of Alzheimer’s disease.

3. Calcium dysregulation in neurodegenerative diseases

Alterations in neural cell calcium homeostasis are characteristic of many neurodegenerative diseases, including Alzheimer’s disease and severalrelated dementias. We are interested in how alterations in intracellular calcium affect particular signaling pathways that are known to play roles in the development of neurodegenerative diseases. We are currently investigating the role of specific native ion channels, and the effect of Ab on calcium signaling pathways that affect tau processing and function.