Premium
P1‐232: A BRAIN REGION SPECIFIC EXPRESSION OF PARASPECKLES PROTEINS IN BRAIN OF MICE MODELED FOR AD
Author(s) -
Shi Lili,
Zheng Baoying,
Su Xiao,
Mo Yin-Yuan,
Wang Jun Ming
Publication year - 2018
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.2018.06.237
Subject(s) - western blot , neurodegeneration , oxidative stress , hippocampal formation , microbiology and biotechnology , apoptosis , chemistry , biology , pathology , neuroscience , biochemistry , medicine , disease , gene
Background: Prolyl-somerases, key enzymes in the folding of nascent polypeptide chains were tested for their ability to interact with and unfold tau aggregates.Methods:In vitro analyses, including thioflavin T fluorescence, NMR, and electronmicrosopy were used to determine the effect of prolyl-isomerases on the kinetics of tau aggregation and disaggregation. An inducible cell model, which overexpresses human tau P301L was used to determine the effect of prolyl-isomerases on sarkosyl soluble and insoluble tau levels after transfection with various prolyl-isomerases. Finally a mouse model of tauopathy (rTg4510) was used to assess behavioral differences, neuronal preservation, and tau levels (silver positive and oligomeric) after hippocampal injection of AAV9-prolyl-isomerases. Results: Biochemical analyses reveal a significant decrease in amyloid content after tau fibrils are incubated with two different prolyl-isomerases. Cell models confirm this result as prolyl-isomerase transfection leads to a significant decrease in sarkosyl insoluble tau by western blot. A mousemodel of tauopathy shows significant rescue of behavioral deficits, neuronal preservation, and significant decreases in both tangles and oligomeric tau species. Conclusions: Some prolyl-isomerases decrease insoluble and oligomeric tau leading to significant reductions in tau-induced pathology. These enzymes therefore represent a new therapeutic in the battle against tauopathies.