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Honokiol and Pioglitazone Ameliorate Alzheimer's Disease Pathologies in vitro and ex vivo
Author(s) -
Lynd Tyler,
Govindarajulu Manoj,
Dhanasekaran Murali,
Suppiramaniam Vishnu
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.552.4
Subject(s) - long term potentiation , agonist , pharmacology , hippocampal formation , neuroscience , ex vivo , chemistry , receptor , biology , medicine , in vivo , microbiology and biotechnology
Amyloid beta (AB) plaques are extracellular, neurotoxic protein aggregations. These plaques have historically been considered the hallmark of Alzheimer's disease due to their ability to reduce long term potentiation (LTP) and promote long term depression (LTD). Peroxisome proliferator‐activated receptor gamma (PPARg) agonists have been shown to be a novel and promising class of drugs capable of alleviating AD pathologies. In this study, we observed the neurotoxic effects of amyloid beta on hippocampal field potentials on the Schaffer collateral. In addition, we displayed honokiol, a novel SIRT3 and partial PPARg agonist, and pioglitazone, a full PPARg agonist, is capable of improving mitochondrial function, increasing LTP, and reducing AB aggregation. The hippocampal field potential along the Schaffer collateral was measured by the LTP theta burst protocol, while signaling mechanisms were evaluated using western blot, RT‐qPCR, mitochondrial assays, and imaging techniques. We hypothesize and provide evidence that these compounds regulate mitochondria‐endoplasmic reticulum communication in order to modify AD pathologies providing evidence for the MAM hypothesis. Both compounds performed comparably suggesting honokiol may be a promising compound for the treatment of AD as its blood brain barrier (BBB) permeability is much higher than pioglitazone. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .