Neurodegeneration in a Drosophila model for the function of TMCC2, an amyloid protein precursor-interacting and apolipoprotein E-binding protein.

ABSTRACT: We previously identified TMCC2 as a protein that interacted differentially with normal versus Alzheimer's disease-risk forms of both apolipoprotein E (apoE) and the amyloid protein precursor (APP). We hypothesized that disrupted function of TMCC2 would affect neurodegeneration. To test this hypothesis, we investigated the Drosophila orthologue of TMCC2, that we have named Dementin. We showed that Dementin interacts genetically both with human APP and its Drosophila orthologue, the APP-like protein (APPL). Ectopic expression of Dementin in Drosophila rescued developmental and behavioral defects caused by expression of human APP. Both a hypomorphic lethal mutation in the dementin gene (dmtn(1)) and RNAi for Dementin caused the accumulation of fragments derived from APPL. We found that Dement

SUBMITTER: Hopkins PC 

PROVIDER: S-EPMC3567013 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature