Overview

Mayo Clinic's Molecular Neurotherapeutics Laboratory, led by Tsuneya Ikezu, M.D., Ph.D., identifies target molecules and cell types and develops therapies to treat or prevent neurodegenerative conditions. These conditions include Alzheimer's disease and other tauopathies, such as frontotemporal lobar degeneration, Lewy body dementia, corticobasal degeneration and progressive supranuclear palsy.

Neurodegenerative disorders

The primary focus of Dr. Ikezu's lab is to understand how tau protein propagates in a stereotypical manner in the brain of patients with Alzheimer's disease and tauopathies. Dr. Ikezu's team identified that microglia and extracellular vesicles mediate the spread of pathogenic tau protein in animal models of Alzheimer's disease.

The team also characterizes lipidomic and proteomic profiles of extracellular vesicles isolated from human brain tissues and biofluids to determine their role in disease spread, intercellular communications and biomarker discovery. This work is done in collaboration with investigators who have expertise in advanced mass spectrometry.

Human-induced pluripotent stem cell (iPSC) research

Human iPSCs are powerful tools for reconstituting the interaction of human neuronal and immune cells in tissue culture models. We are remodeling the central nervous system (spheroids), which consists of many neuronal cell types, using human iPSCs derived from people with illness and those without. These models are being tested using confocal microscopy, electrophysiology, RNA sequencing and proteomics. Moreover, we perform CRISPR editing of the iPSC genome and differentiate human microglia or oligodendrocytes that are adapted to survive in neurodegenerative conditions. The goal is to develop next-generation biotherapeutics.

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