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PPARs in the central nervous system: roles in neurodegeneration and neuroinflammation
Author(s) -
Zolezzi Juan M.,
Santos Manuel J.,
BastíasCandia Sussy,
Pinto Claudio,
Godoy Juan A.,
Inestrosa Nibaldo C.
Publication year - 2017
Publication title -
biological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.993
H-Index - 165
eISSN - 1469-185X
pISSN - 1464-7931
DOI - 10.1111/brv.12320
Subject(s) - neuroinflammation , neurodegeneration , neuroprotection , nuclear receptor , ppar agonist , biology , peroxisome proliferator activated receptor , receptor , microbiology and biotechnology , neuroscience , transcription factor , lipid metabolism , inflammation , immunology , medicine , biochemistry , disease , gene
Over 25 years have passed since peroxisome proliferators‐activated receptors ( PPARs ), were first described. Like other members of the nuclear receptors superfamily, PPARs have been defined as critical sensors and master regulators of cellular metabolism. Recognized as ligand‐activated transcription factors, they are involved in lipid, glucose and amino acid metabolism, taking part in different cellular processes, including cellular differentiation and apoptosis, inflammatory modulation and attenuation of acute and chronic neurological damage in vivo and in vitro . Interestingly, PPAR activation can simultaneously reprogram the immune response, stimulate metabolic and mitochondrial functions, promote axonal growth, induce progenitor cells to differentiate into myelinating oligodendrocytes, and improve brain clearance of toxic molecules such as β‐amyloid peptide. Although the molecular mechanisms and cross‐talk with different molecular pathways are still the focus of intense research, PPAR s are considered potential therapeutic targets for several neuropathological conditions, including degenerative disorders such as A lzheimer's, P arkinson's and H untington's disease. This review considers recent advances regarding PPARs , as well as new PPAR agonists. We focus on the mechanisms behind the neuroprotective effects exerted by PPARs and summarise the roles of PPARs in different pathologies of the central nervous system, especially those associated with degenerative and inflammatory mechanisms.