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

Senn, Lara; Costa, Anna‐Maria; Avallone, Rossella; Socała, Katarzyna; Właź, Piotr; Biagini, Giuseppe

doi:10.1016/j.pharmthera.2022.108316

Cited by 10 publications

(3 citation statements)

References 255 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is plausible that CBD prolongs survival of these mice by exerting anticonvulsant activities largely via PPARγ activation. Accordingly, compelling evidence indicates that PPARγ might be a potential target for patients with epilepsy, especially for those who are treatment-resistant or at high risk to develop fatal events (see 68 for review). Indeed, several preclinical studies have investigated the effect of well-established PPARγ agonists thiazolidinediones and showed antiseizure activity 68 .…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, compelling evidence indicates that PPARγ might be a potential target for patients with epilepsy, especially for those who are treatment-resistant or at high risk to develop fatal events (see 68 for review). Indeed, several preclinical studies have investigated the effect of well-established PPARγ agonists thiazolidinediones and showed antiseizure activity 68 . Moreover, PPARγ expression levels also seem to play a key role.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cannabidiol ameliorates mitochondrial disease via PPARγ activation

Quintana,

Puighermanal,

Luna-Sánchez

et al. 2023

Preprint

View full text Add to dashboard Cite

Mutations in mitochondrial energy-producing genes lead to a heterogeneous group of untreatable disorders known as primary mitochondrial diseases (MD). Leigh syndrome (LS) is the most common pediatric MD and is characterized by progressive neuromuscular affectation and premature death. Here, we show that daily cannabidiol (CBD) administration significantly extends lifespan and ameliorates pathology in two LS mouse models, and cellular function in fibroblast from LS patients. CBD delays motor decline and neurodegenerative signs, improves social deficits and breathing abnormalities, decreases thermally induced seizures, and improves neuropathology in affected brain regions. Mechanistically, we identify peroxisome proliferator-activated receptor gamma (PPARγ) as a key contributor to CBD’s beneficial effects, and provide proof of dysregulated PPARγ expression and activity as a common feature in both mouse neurons and fibroblasts from LS patients. Taken together, our results provide the first evidence for CBD as a potential treatment for LS.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cannabidiol ameliorates mitochondrial disease via PPARγ activation

Quintana,

Puighermanal,

Luna-Sánchez

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Moreover, PPARγ has been recently suggested as a putative target for epilepsy treatment [ 23 ]. PPARγ could also be involved in the modulation of the anticonvulsant effects of EP-80317, a ghrelin receptor antagonist [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory, Antioxidant, and WAT/BAT-Conversion Stimulation Induced by Novel PPAR Ligands: Results from Ex Vivo and In Vitro Studies

et al. 2023

View full text Add to dashboard Cite

Activation of peroxisome proliferator-activated receptors (PPARs) not only regulates multiple metabolic pathways, but mediates various biological effects related to inflammation and oxidative stress. We investigated the effects of four new PPAR ligands containing a fibrate scaffold—the PPAR agonists (1a (αEC50 1.0 μM) and 1b (γEC50 0.012 μM)) and antagonists (2a (αIC50 6.5 μM) and 2b (αIC50 0.98 μM, with a weak antagonist activity on γ isoform))—on proinflammatory and oxidative stress biomarkers. The PPAR ligands 1a-b and 2a-b (0.1–10 μM) were tested on isolated liver specimens treated with lipopolysaccharide (LPS), and the levels of lactate dehydrogenase (LDH), prostaglandin (PG) E2, and 8-iso-PGF2α were measured. The effects of these compounds on the gene expression of the adipose tissue markers of browning, PPARα, and PPARγ, in white adipocytes, were evaluated as well. We found a significant reduction in LPS-induced LDH, PGE2, and 8-iso-PGF2α levels after 1a treatment. On the other hand, 1b decreased LPS-induced LDH activity. Compared to the control, 1a stimulated uncoupling protein 1 (UCP1), PR-(PRD1-BF1-RIZ1 homologous) domain containing 16 (PRDM16), deiodinase type II (DIO2), and PPARα and PPARγ gene expression, in 3T3-L1 cells. Similarly, 1b increased UCP1, DIO2, and PPARγ gene expression. 2a-b caused a reduction in the gene expression of UCP1, PRDM16, and DIO2 when tested at 10 μM. In addition, 2a-b significantly decreased PPARα gene expression. A significant reduction in PPARγ gene expression was also found after 2b treatment. The novel PPARα agonist 1a might be a promising lead compound and represents a valuable pharmacological tool for further assessment. The PPARγ agonist 1b could play a minor role in the regulation of inflammatory pathways.

show abstract