QnAs with Linda Hsieh-Wilson

Abstract

Since the 1890s, neuroscientists have known that the space between neurons, the extracellular matrix, plays a crucial role in brain function. Early brain anatomists uncovered specialized substructures of the brain's extracellular matrix called perineuronal nets, which can constrain neuronal activity. However, it was not until decades later that the molecular composition of these structures was unraveled. The structures were found to be primarily composed of a mix of proteins and carbohydrates, called proteoglycans. California Institute of Technology biochemist Linda Hsieh-Wilson investigates how posttranslational modifications to proteoglycans affect brain function. Her group has developed chemical and informatics tools that demonstrate that specific sulfation pathways contribute to neuronal functions such as social memory. They have also linked these pathways to neurological and neuropsychiatric disorders such as Alzheimer's disease, schizophrenia, and depression. Hsieh-Wilson was elected to the National Academy of Sciences in 2022. PNAS recently spoke to her about her current research.

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