CENTRAL TIME

Claudio Marcelo Aldaz, MD, PhD will present the research, “Role of WWOX loss-of-function in progressive cerebellar ataxia and neurodegeneration.”

Science Showcase sessions explore a past NAF research grant awardee’s funded study to gain scientific insights about their Ataxia research.

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Lay Summary: Our preliminary data indicates that partial WWOX LoF is sufficient to induce ataxia, epilepsy, and progressive cerebellar degeneration. We hypothesize that WWOX function deficiency leads to alterations in neuronal differentiation and function while also enhancing neuroimmune activation. Thus, in Aim 1 of this proposal, we will characterize the cellular and structural abnormalities cause in mouse brain by the described SCAR12 WWOX partial LoF mutation with particular emphasis in cerebellum. We also hypothesize that impaired WWOX function alters neuronal cell differentiation and function in cerebellum, thus in Aim 2, we will investigate the effects of the SCAR12 mutation in the expression of all other genes in the various cerebellum’s cell types. To that end we will use state-of-the-art molecular approaches to analyze gene expression at the single cell level. This information will allow us to build molecular networks relevant to WWOX LoF in ataxia pathogenesis. In Aim 3 we will evaluate the effects of WWOX deficiency in neuronal and glial differentiation using neural stem cells neurospheres from mouse brain.

Impact: Understanding the intriguing role of WWOX LoF in conditions associated with ataxia and neurodegeneration has the potential of leading to novel rationale based therapeutic interventions.