Is the peroxisome proliferator-activated receptor gamma a putative target for epilepsy treatment? Current evidence and future perspectives

• Published in: Pharmacology & therapeutics (Oxford) Vol. 241; p. 108316
• Main Authors: Senn, Lara, Costa, Anna-Maria, Avallone, Rossella, Socała, Katarzyna, Wlaź, Piotr, Biagini, Giuseppe
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01-01-2023
• Subjects: Anticonvulsant; Antiseizure medications; Epilepsy; Epilepsy - drug therapy; Humans; Peroxisome proliferator-activated receptor gamma; PPAR gamma - agonists; PPAR gamma - metabolism; Seizure; Thiazolidinediones; Thiazolidinediones - therapeutic use; aP2; DBA; FAAH; BBB; PTEN; LBD; BSA; NF-κB; TZDs; CA3; PI3K; AME; iNOS; Seizure; CD36; TRIM27; AEA; MCAD; AA; l-NAME; SRC1/2/3; i.p; Antiseizure medications; PPREs; PPARγ; i.v; FABPs; CB1; MMP-2/9/13; 2-AG; GABA; SRSs; BHB; CPT-1; NADPH; VEGFR2; PGC1α/β; CBD; COX-2; Epilepsy; CNS; Anticonvulsant; HO-1; TLE; RXR; CBP; nuclear receptors; SE; Nrf2; KA; PTZ; KD; ASM; ACA; IL-1β,6,10; Peroxisome proliferator-activated receptor gamma; BDNF; FMOC-L-leucine; SOD; UCP-2; CO; p.o; TrkB; SUDEP; TNF-α; AF-1/2; Bax; PUFAs; Thiazolidinediones; CYP4A
• ISSN: 0163-7258; 1879-016X
• DOI: 10.1016/j.pharmthera.2022.108316

The peroxisome proliferator-activated receptor gamma (PPARγ), which belongs to the family of nuclear receptors, has been mainly studied as an important factor in metabolic disorders. However, in recent years the potential role of PPARγ in different neurological diseases has been increasingly investigated. Especially, in the search of therapeutic targets for patients with epilepsy the question of the involvement of PPARγ in seizure control has been raised. Epilepsy is a chronic neurological disorder causing a major impact on the psychological, social, and economic conditions of patients and their families, besides the problems of the disease itself. Considering that the world prevalence of epilepsy ranges between 0.5% - 1.0%, this condition is the fourth for importance among the other neurological disorders, following migraine, stroke, and dementia. Among others, temporal lobe epilepsy (TLE) is the most common form of epilepsy in adult patients. About 65% of individuals who receive antiseizure medications (ASMs) experience seizure independence. For those in whom seizures still recur, investigating PPARγ could lead to the development of novel ASMs. This review focuses on the most important findings from recent investigations about the potential intracellular PPARγ-dependent processes behind different compounds that exhibited anti-seizure effects. Additionally, recent clinical investigations are discussed along with the promising results found for PPARγ agonists and the ketogenic diet (KD) in various rodent models of epilepsy.