PPARs, Psychoneuroimmunology, and Potential Treatment of Psychiatric Disorders

Peroxisome Proliferator-Activated Receptors (PPARs) are a group of transcription factors that play important roles in glucose homeostasis, fatty acid and lipoprotein metabolism, and immune responses (Rolland et al., 2013). They are involved in the regulation of cellular proliferation and differentiation, blood pressure, nerve-cell protection, as well as the inflammatory pathways (Menendez-Gutierrez et al., 2012).

PPARs have been used as critical drug targets for treating metabolic disorders including type 2 diabetes and insulin resistance. Because of their associations with inflammation, PPARs have also been considered useful for the treatment of chronic inflammatory disorders including atherosclerosis, inflammatory bowel disease, pancreatitis, lung problems such as chronic pulmonary inflammation, autoimmune diseases such as arthritis, and skin problems such as psoriasis (Menendez-Gutierrez et al., 2012).

In addition, PPARs have been connected to the modulation of neuroinflammation, inflammatory pain reduction, and the hypothalamic regulation of metabolism (Menendez-Gutierrez et al., 2012). Furthermore, they have been found to be involved in the regulation of neurotransmission factor expressions (Rolland et al., 2013). These multiple functions of PPARs have suggested their potential therapeutic power.

For example, inflammatory processes have been found to be crucial in psychiatric disorders including mood disorders and schizophrenia. Based on such findings, novel medications may be developed to target PPARs for the regulation of information processing and the treatment of these psychiatric disorders. Their roles in metabolic regulation may also be helpful for the prevention of the metabolic adverse reactions in traditional psychiatric medications such as antipsychotics (Rolland et al., 2013).

However, because of the non-specific targeting actions, available PPAR-based medications often lead to unwanted side effects. With the development in the field of psychoneuroimmunology, PPAR-based therapies can be improved such as by using cell-specific PPAR agonists (Rolland et al., 2013; Menendez-Gutierrez et al., 2012). In summary, the multiple functions of PPAR ligands have indicated their potential therapeutic prospects for the treatment of a broad range of diseases that are associated with chronic inflammation, from metabolic disorders to psychiatric disorders, from cardiovascular disease to cancer.

References:

Menendez-Gutierrez MP, Roszer T, Ricote M. Biology and therapeutic applications of peroxisome proliferator- activated receptors. Curr Top Med Chem.  2012;12(6):548-84.

Rolland B, Deguil J, Jardri R, Cottencin O, Thomas P, Bordet R. Therapeutic prospects of PPARs in psychiatric disorders: a comprehensive review. Curr Drug Targets. 2013 Jun;14(7):724-32.

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