Unlike PPARgamma, neither other PPARs nor PGC-1alpha is elevated in the cerebrospinal fluid of patients with multiple sclerosis

Szalárdy, Levente and Zádori, Dénes and Bencsik, Krisztina and Vécsei, László and Klivényi, Péter (2017) Unlike PPARgamma, neither other PPARs nor PGC-1alpha is elevated in the cerebrospinal fluid of patients with multiple sclerosis. NEUROSCIENCE LETTERS, 651. pp. 128-133. ISSN 0304-3940

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Abstract

Corroborating with prior experimental findings, we recently reported the pronounced elevation of peroxisome proliferator-activated receptor gamma (PPARgamma) protein concentration in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS), in association with neuroinflammatory markers and clinical severity. Based on subsequent reports on the possible involvement of other PPARs and PPARgamma coactivator-1alpha (PGC-1alpha) in neuroinflammation in MS, we analyzed the protein levels of PPARalpha, PPARbeta/delta, and PGC-1alpha in a subset of CSF samples from the same cohort of relapsing-remitting MS patients. Unlike PPARgamma, none of these proteins were found elevated in MS patients (n=25) compared to non-inflammatory controls (n=16), with the levels of PPARalpha and PPARbeta/delta found generally below the limit of detection, and that of PGC-1alpha being detectable but comparable in both groups. The clinical and laboratory associations previously reported with PPARgamma were however significant even in this smaller subset. The potential underlying causes of these differential alterations are discussed. The findings suggest that despite their proposed involvement in the regulation of inflammatory processes in MS, PPARalpha, PPARbeta/delta, and PGC-1alpha proteins are not potential biomarkers of neuroinflammation in MS, and indicate a preferential role of PPARgamma in the endogenous regulation of autoimmune response in the human CNS within its receptor family.

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