Principal Investigators

    BOSCO, DARYL ANGELA

    Institution

    UNIV OF MASSACHUSETTS MED SCH WORCESTER

    Contact information of lead PI

    Country

    USA

    Title of project or programme

    Investigating the response of FUS/TLS to excitotoxic insult

    Source of funding information

    NIH (NINDS)

    Total sum awarded (Euro)

    422591.7431

    Start date of award

    15/09/2015

    Total duration of award in years

    1

    Keywords

    Amyotrophic Lateral Sclerosis, excitotoxicity, RNA-Binding Protein FUS, Glutamates, liposarcoma

    Research Abstract

    ? DESCRIPTION (provided by applicant): Fused in Sarcoma/Translocated in Liposarcoma (FUS/TLS or FUS) is a multifunctional, RNA/DNA-binding protein that is pathologically associated with amyotrophic lateral sclerosis (ALS). The role of FUS in this disorder has not been elucidated, although evidence exists to support both a loss of normal FUS function and gain of toxic function mechanisms. We have identified a novel, normal response of FUS to excitotoxic levels of glutamate in primary neurons. Our preliminary data demonstrates that endogenous FUS translocates from the nucleus to the cytoplasm in response to sublethal but excitotoxic levels of glutamate. Glutamate excitotoxicity is strongly implicated in ALS, and therefore we believe these finding are relevant to disease pathogenesis. We posit that FUS plays a normal and protective role in response to excitotoxicity, which is a form of cellular stres. Our hypothesis is that FUS functions in the context of protein translation in response to excitotoxic stress. This response may be impaired by ALS-causing mutations, thereby exacerbating the severity of excitotoxicity in FUS-mediated ALS. Moreover, chronic excitotoxicity may contribute to the accumulation and subsequent aggregation of the FUS protein in diseased neurons. The Aims of this proposal will investigate the response of FUS to excitotoxic levels of glutamate in neurons and determine if ALS-linked mutations alter this response.

    Further information available at:

Types: Investments < €500k
Member States: United States of America
Diseases: N/A
Years: 2016
Database Categories: N/A
Database Tags: N/A

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