Principal Investigators

    C. O'Neil, R.Sims

    Institution

    Multiple

    Contact information of lead PI

    Country

    Ireland|United Kingdom

    Title of project or programme

    Therapeutic targeting of impaired lysosomal flux in Alzheimer's disease

    Source of funding information

    CoEN

    Total sum awarded (Euro)

    € 379,112

    Start date of award

    01/06/2018

    Total duration of award in years

    2

    Keywords

    Research Abstract

    There are currently no effective treatments for Alzheimer’s disease (AD). Novel approaches are urgently needed.
    Innovative systems that increase the clearance of disease-associated proteins in and around brain cells are one such approach. Increased clearance of these proteins via lysosomal flux show extremely encouraging results in AD animal models, clearing the two hallmark brain changes that define AD, deposition of amyloid-beta-protein (Abeta) and tau.
    However, therapeutic targets which will selectively modify lysosomal flux to prevent these brain changes are lacking. Our previous research indicates that the lysosomal Ca2+ release channel protein, TRPML1, has major potential as such a target.
    This proposal will use our multidisciplinary expertise to determine the therapeutic potential of TRPML1 in AD. TRPML1 is easily targetable and selectively activated/inactivated by lipid molecules called the phosphoinositides (PI), specifically PI(3,5)P2 and PI(4,5)P2, respectively.
    Many previously identified AD risk genes bind to PI(4,5)P2 (including ApoE4, PICALM, BIN1, CD2AP). Another AD risk gene can alter PI(4,5)P2 metabolism (INN5PD). We will test the hypothesis that these previously identified risk genes regulate phosphinositide activity to contribute to AD pathology by altering TRPML-1 mediated lysosomal flux, and determine whether targeting this TRPML1 defect offers therapeutic potential for AD. Combining a multi-disciplined approach involving our expertise in AD neuropathology, TRPML1 function, lysosomal flux and AD genetics, this research presents an exciting opportunity to develop novel disease-modifying therapeutic/diagnostic platforms with selective innovative targeting of lysosomal flux defects to combat AD pathogenesis in populations worldwide.

    Further information available at:

Types: Investments < €500k
Member States: Ireland, United Kingdom
Diseases: N/A
Years: 2016
Database Categories: N/A
Database Tags: N/A

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