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Sarah Hernandez Neurobiology & Behavior Mentor: Leslie Thompson |
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Summary |
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Huntington’s disease (HD) is a progressive, neurodegenerative disorder caused by a genetic expansion of a CAG repeat encoding glutamine within the huntingtin protein. Individuals with 40 or more glutamines will eventually develop HD. HD is devastating, causing atrophy of the brain, uncontrollable movements, psychiatric disturbances, and behavioral changes. The extracellular matrix (ECM) is a highly plastic component of the cellular environment, continuously being remodeled by architectural modifications that guide cell attachment, cell motility, and cell survival. In the brain, the ECM can provide neuroprotection and loss of certain ECM components leads to phenotypes commonly observed in neurodegenerative diseases. Additionally, perturbations of the ECM can alter synaptic plasticity in the adult brain. And while there is clear evidence regarding the importance of ECM participation in critical CNS functions and neuronal dynamics, little is known about the role of the ECM in neurodegenerative diseases, including HD. Additionally, ECM molecules have shown great promise as highly druggable targets for diseases associated with traumatic neuronal loss. Therefore, taking advantage of the malleability of the ECM and the influence it has on neural plasticity through exogenous introduction of ECM molecules or agonists may allow for the prevention or reversal of disease-associated changes in the HD brain. Identification of ECM disease regulators provides molecular targets that can then be perturbed within cellular systems to elicit disease-modifying effects. |
