Elevated levels of PPAR-gamma in the cerebrospinal fluid of patients with multiple sclerosis

Szalárdy, Levente; Zádori, Dénes; Tánczos, Ervin; Simu, Mihaela; Bencsik, Krisztina; Vécsei, László; Klivényi, Péter

doi:10.1016/j.neulet.2013.08.069

Cited by 25 publications

(18 citation statements)

References 38 publications

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“…Analogously, owing to their engagement in the regulation of neuroinflammation and innate immune response, PPAR dysfunction may play a role in the molecular mechanisms that trigger multiple sclerosis (MS) [129,130]. Interestingly, in PBMC of patients affected by MS, PPAR-γ expression was decreased [131,132].…”

Section: Neurological Disordersmentioning

confidence: 99%

Is There a Future for PPARs in the Treatment of Neuropsychiatric Disorders?

Tufano

Pinna

2020

Molecules

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Recently, peroxisome proliferator-activated receptor (PPAR)-α and γ isoforms have been gaining consistent interest in neuropathology and treatment of neuropsychiatric disorders. Several studies have provided evidence that either the receptor expression or the levels of their endogenously-produced modulators are downregulated in several neurological and psychiatric disorders and in their respective animal models. Remarkably, administration of these endogenous or synthetic ligands improves mood and cognition, suggesting that PPARs may offer a significant pharmacological target to improve several neuropathologies. Furthermore, various neurological and psychiatric disorders reflect sustained levels of systemic inflammation. Hence, the strategy of targeting PPARs for their anti-inflammatory role to improve these disorders is attracting attention. Traditionally, classical antidepressants fail to be effective, specifically in patients with inflammation. Non-steroidal anti-inflammatory drugs exert potent antidepressant effects by acting along with PPARs, thereby strongly substantiating the involvement of these receptors in the mechanisms that lead to development of several neuropathologies. We reviewed running findings in support of a role for PPARs in the treatment of neurological diseases, including Alzheimer’s disease or psychiatric disorders, such as major depression. We discuss the opportunity of targeting PPARs as a future pharmacological approach to decrease neuropsychiatric symptoms at the same time that PPAR ligands resolve neuroinflammatory processes.

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Section: Neurological Disordersmentioning

confidence: 99%

Is There a Future for PPARs in the Treatment of Neuropsychiatric Disorders?

Tufano

Pinna

2020

Molecules

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“…A recent study demonstrated that a ligand-activated transcription factor known as peroxisome proliferator-activated receptor gamma (PPARγ) playing a pivotal role in regulation of glucose and lipid metabolism is markedly increased in CSF of MS patients ( 27 ). Furthermore, elevated expression of PPARγ has been reported within the spinal cord of EAE mice ( 28 ) and in an in vitro model of antigen induced demyelination ( 29 ).…”

Section: Glucose Metabolism and Multiple Sclerosismentioning

confidence: 99%

Perturbed Glucose Metabolism: Insights into Multiple Sclerosis Pathogenesis

et al. 2014

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Multiple sclerosis (MS) is a complex debilitating disease of the central nervous system (CNS) perceived to result from the autoimmune effect of T cells in damaging myelin sheath. However, the exact pathogenesis of the disease remains elusive. Initial studies describing the possibility of defective pyruvate metabolism in MS were performed in 1950s. The group observed elevated blood pyruvate level in both fasting and postprandial times in MS patients with relapse. Similarly, other investigators also reported increased fasting pyruvate level in this disease. These reports hint to a possible abnormality of pyruvate metabolism in MS patients. In addition, increase in levels of Krebs cycle acids like alpha-ketoglutarate in fasting and citrate after glucose intake in MS patients further strengthened the connection of disturbed pyruvate metabolism with MS progression. These studies led the investigators to explore the role of disturbed glucose metabolism in pathophysiological brain function. Under normal circumstances, complex molecules are metabolized into simpler molecules through their respective pathways. Differential expression of genes encoding enzymes of the glucose metabolic pathway in CNS may result in neurological deficits. In this review article, we discuss the studies related to disturbed carbohydrate metabolism in MS and other neurodegenerative diseases. These observations open new perspectives for the understanding of metabolic dynamics in MS yet many puzzling aspects and critical questions need to be addressed. Much more research is required to fully unravel the disease mechanism, and a proper understanding of the disease could eventually lead to new treatments.

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“…In this regard, it is interesting that PPAR γ may regulate the expression of β 1 integrin [13]. Moreover, in MS patients free of therapy, a pronounced elevation of PPAR γ levels in the cerebrospinal fluid (CSF) was associated with increased intrathecal inflammation [14]. Overall, these data suggest that PPAR γ -mediated processes may contribute to the mechanism of action of NTZ.…”

Section: Discussionmentioning

confidence: 99%

Natalizumab Treatment Modulates Peroxisome Proliferator-Activated Receptors Expression in Women with Multiple Sclerosis

et al. 2016

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Peroxisome Proliferator-Activated Receptors (PPAR) are transcription factors suggested to be involved in inflammatory lesions of autoimmune encephalomyelitis and multiple sclerosis (MS). Our objective was to assess whether Natalizumab (NTZ) therapy is associated with alterations of PPAR expression in MS patients. We analyzed gene expression of PPAR in peripheral blood mononuclear cells (PBMC) as well as blood inflammatory markers in women with MS previously medicated with first-line immunomodulators (baseline) and after NTZ therapy. No differences in PPARα, PPARβ/δ, PPARγ, and CD36 mRNA expression were found in PBMC between patients under baseline and healthy controls. At three months, NTZ increased PPARβ/δ mRNA (p = 0.009) in comparison to baseline, while mRNA expression of PPARγ and CD36 (a well-known PPAR target gene) was lower in comparison to healthy controls (p = 0.026 and p = 0.028, resp.). Although these trends of alterations remain after six months of therapy, the results were not statistically significant. Osteopontin levels were elevated in patients (p = 0.002) and did not change during the follow-up period of NTZ treatment. These results suggest that PPAR-mediated processes may contribute to the mechanisms of action of NTZ therapy.

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Elevated levels of PPAR-gamma in the cerebrospinal fluid of patients with multiple sclerosis

Cited by 25 publications

References 38 publications

Is There a Future for PPARs in the Treatment of Neuropsychiatric Disorders?

Is There a Future for PPARs in the Treatment of Neuropsychiatric Disorders?

Perturbed Glucose Metabolism: Insights into Multiple Sclerosis Pathogenesis

Natalizumab Treatment Modulates Peroxisome Proliferator-Activated Receptors Expression in Women with Multiple Sclerosis

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