Premium
P4–287: A general amyloid interaction motif (GAIM) approach to targeting multiple types of misfolded protein deposits in models of neurodegenerative disease
Author(s) -
Masliah Eliezer,
Rockenstein Edward,
Fisher Richard,
Levenson Jonathan,
Gan Kimberley
Publication year - 2013
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2013.05.1680
Subject(s) - neuropathology , genetically modified mouse , alpha synuclein , protein aggregation , transgene , neuroscience , amyloid (mycology) , neurodegeneration , disease , biology , chemistry , medicine , parkinson's disease , microbiology and biotechnology , pathology , gene , biochemistry
Misfolded protein aggregates play a central role in the pathobiology of neurodegenerative diseases, including Parkinson’s disease and Alzheimer’s disease. Evidence from imaging and neuropathology studies show that brains from neurodegenerative disease sufferers can contain two or more pathological misfolded protein aggregates, which, taken together with biochemical evidence, suggests aggregate cross-seeding and synergistic neurotoxicity. Furthermore, emerging data suggest that single target approaches for lowering pathological aggregate loads may not offer sufficient clinical benefit to support further development. We have shown that the native filamentous bacteriophage M13 (NPT001/NPT002) is an effective treatment for lowering multiple species of brain aggregates in transgenic models. The mechanism for the amyloid-targeting activity has been elucidated and a fragment of a capsid protein, called the General Amyloid Interaction Motif or GAIM, has been shown to recapitulate the phage activities in biochemical (Poster P2-050) and animal model assays (Poster P4-290).