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@INPROCEEDINGS{AlfonsoPrieto:1024689,
author = {Alfonso-Prieto, Mercedes and Müller, Nicolas and Sergeeva,
Olga A. and Navarini, Luciano and Carloni, Paolo},
title = {{M}olecular insights into the neuroprotective effects of
chlorogenic acids mediated by the peroxisome
proliferator-activated receptor {PPAR}alpha},
issn = {0006-3495},
reportid = {FZJ-2024-02362},
year = {2024},
abstract = {The peroxisome proliferator-activated receptor PPARalpha
has been associated to neuroprotection against Parkinson’s
and Alzheimer’s diseases [1]. PPARalpha binds a wide
variety of ligands [2], including FDA-approved drugs,
suggesting that PPARalpha could be used as an alternative
therapeutic target against neurodegeneration. Endogenous
ligands of PPARalpha include fatty acids (such as oleic
acid, whose concentration is pathologically increased in
several neurodegenerative diseases) and their derivatives
(such as OLHA, the conjugate of oleic acid and histamine)
[3]. In addition, PPARalpha exogenous ligands span from
drugs against diabetes and hyperlipidemia to food molecules,
such as cinnamic acid [4-5] and the closely related
chlorogenic acids (CGAs). Using molecular simulations, we
have investigated the binding determinants of CGA-related
compounds. Our computational results, in combination with
experiments on brain slices, show that these novel PPARalpha
ligands could bind to the receptor similarly to known
endogenous agonists and drugs. In the long term, this
molecular information may be used as a stepping stone for
designing PPARalpha-based neuroprotective therapies.[1]
Willems S. et al. (2021) J. Med. Chem. 64:9592–9638.[2]
Kamata S. et al. (2020) iScience 23:101727.[3] Sergeeva O.A.
(2022) Neuropharmacology 215:109167.[4] Chandra S. et al.
(2019) Neurobiol. Dis. 124:379–395.[5] Prorok T. et al.
(2019) Neurochem. Res. 44(4):751–762.},
month = {Feb},
date = {2024-02-10},
organization = {Biophysical Society Meeting,
Philadelphia (USA), 10 Feb 2024 - 14
Feb 2024},
subtyp = {After Call},
cin = {IAS-5 / INM-9},
ddc = {570},
cid = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)INM-9-20140121},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524) / 5252 - Brain Dysfunction and Plasticity
(POF4-525)},
pid = {G:(DE-HGF)POF4-5241 / G:(DE-HGF)POF4-5252},
typ = {PUB:(DE-HGF)24},
url = {https://juser.fz-juelich.de/record/1024689},
}