1. Neuronal calcium signaling as therapeutic target for Alzheimer’s disease.
Dysregulation of neuronal calcium signaling is one of the key features and likely driver of pathology in Alzheimer’s disease (AD). Our laboratory discovered the essential role of presenilins in neuronal calcium homeostasis. We continue to explore a variety of calcium channels, transporters and calcium signaling molecules as potential therapeutic targets for AD treatment. We reason that this approach may lead to the development of novel disease-modifying agents for AD that can be used as monotherapy or in combination with anti-amyloid treatments.
2. Sigma 1 receptor – biological function and importance for neurodegeneration.
Normal biological function of Sigma 1 receptors (S1R) is not known. Our laboratory discovered that S1R directly binds to cholesterol and forms cholesterol-enriched microdomains in the endoplasmic reticulum membrane. We continue to develop this idea and explore its importance for neuroprotective effects of S1R agonists in neurodegenerative disease models and clinical trials.
3. Functional approach to developing therapeutic agents for ataxia.
Dysfunction of cerebellar Purkinje cells plays a key role at early stages of spinocerebellar ataxias (SCA). Our laboratory demonstrated that positive allosteric modulators of calcium-activated potassium channels normalize function of Purkinje cells in mouse model of SCA2. Based on these results, we continue to develop and test novel positive allosteric modulators of calcium-activated potassium channels as potential treatment for SCAs.