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

Abstract

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.

Keywords

• ppar-α
• ppar-γ
• neuropsychiatric disorders
• major depression
• alzheimer’s disease
• allopregnanolone
• bdnf
• neuroinflammation
• toll-like receptor