Research Projects

Alzheimer's disease (AD) is a prevalent form of dementia worldwide, with early-stage hyperactivity of brain cells attributed to toxic amyloid β (Aβ) peptide species. Two pore domain leak potassium channels (K2P) are known to decrease neuronal hyperactivity and protect brain cells in neurological disorders like cerebral ischemia. However, the interaction between Aβ and K2P and the mechanisms underlying this interaction remains unknown. The study aims to investigate the interaction between pathological Aβ peptide species and K2P channels, using patch clamp electrophysiology configurations to study the direct/indirect interaction of Aβ with K2P channels like TREK1, TASK1, and TASK3 overexpressed in HEK293 cells. The study will also use molecular biology techniques like immunocytochemistry and qPCR to study changes in expression and mechanisms underlying these changes in K2P in ReNcell VM neural progenitor cell line (ReN) and SH-SY5Y cell line (SH-SY5Y) derived neuronal cells. The expected outcome is that Aβ mediates a decrease in K2P channel activity and expression leading to hyperactivity in AD neurons, suggesting that increasing K2P activity could provide neuroprotection against Aβ mediated excitotoxicity. This research can provide mechanistic insight into contributors of electrical abnormality in AD and identify K2P as novel drug targets for therapeutic intervention.