Minutes of PPAR-γ agonism and neuroprotection

Kumar, B. R. Prashantha; Kumar, Ashwini Prem; Jose, Jincy A.; Prabitha, P.; Sambandam, Yuvaraj; Chipurupalli, Sandhya; Jeyarani, Victoria; Manisha, Chennu; Banerjee, Sandip; Jeyabalan, Jeyaram Bharathi; Mohankumar, Suresh Kumar; Dhanabal, S. P.; Justin, Antony

doi:10.1016/j.neuint.2020.104814

Cited by 39 publications

(28 citation statements)

References 91 publications

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“…Moreover, PPAR-γ has been indicated as a potential target in MDD (Prashantha Kumar et al, 2020;Tufano & Pinna, 2020). Therefore, our results provide additional evidence that RA's antidepressant-like effect may depend on the CB 1 /CB 2 /PPAR-γ signaling pathway.…”

Section: Discussionsupporting

confidence: 56%

“…This receptor is expressed in brain areas (piriform cortex, amygdala, VTA, nucleus accumbens , basal ganglia) and some cell subtypes (dopaminergic neurons, astrocytes, and microglia). Moreover, PPAR‐γ has been indicated as a potential target in MDD (Prashantha Kumar et al, 2020; Tufano & Pinna, 2020). Therefore, our results provide additional evidence that RA's antidepressant‐like effect may depend on the CB 1 /CB 2 /PPAR‐γ signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

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Antidepressant‐like effect of rosmarinic acid during LPS‐induced neuroinflammatory model: The potential role of cannabinoid receptors/PPAR‐γ signaling pathway

Lataliza

Assis

Laurindo

et al. 2021

Phytotherapy Research

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Rosmarinic acid (RA), an ester of caffeic acid and 3, 4-dihydroxyphenyllactic acid, has anti-inflammatory and neuroprotective activities. Herein, this study investigated in silico the drug-likeness and the potential molecular targets to RA. Moreover, it tested the antidepressant-like potential of RA in the lipopolysaccharide (LPS)-induced depression model. RA (MW = 360.31 g/mol) meets the criteria of both Lipinski's rule of five and the Ghose filter. It also attends to relevant pharmacokinetic parameters.Target prediction analysis identified RA's potential targets and biological activities, including the peroxisome proliferator-activated receptor (PPAR) and the cannabinoid receptors CB 1 and CB 2 . In vivo, RA's acute, repetitive, and therapeutic administration showed antidepressant-like effect since it significantly reduced the immobility time in the tail suspension test and increased grooming time in the splash test. Further, the pretreatment with antagonists of CB 1 , CB 2 , and PPAR-γ receptors significantly blocked the antidepressant-like effect of RA. Altogether, our findings suggest that cannabinoid receptors/PPAR-γ signaling pathways are involved with the antidepressant-like effect of RA. Moreover, this molecule meets important physicochemical and pharmacokinetic parameters that favor its bioavailability. RA constitutes a promising, innovative, and safe molecule for the pharmacotherapy of major depressive disorder.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Antidepressant‐like effect of rosmarinic acid during LPS‐induced neuroinflammatory model: The potential role of cannabinoid receptors/PPAR‐γ signaling pathway

Lataliza

Assis

Laurindo

et al. 2021

Phytotherapy Research

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“…For example, EGR1, a transcription factor known to play a role in cellular division, neuronal plasticity, and memory, has been proposed to be associated with ALS risk (Recabarren-Leiva and Alarcon, 2018 ). The involvement of PPARG in neuroprotection has been extensively documented in neurodegenerative diseases (Kiaei, 2008 ; Prashantha Kumar et al, 2020 ). Activation of PPARG has been shown to elicit neuroprotection in drosophila models overexpressing TDP-43 or FUS and in SOD mice models (Kiaei et al, 2005 ; Joardar et al, 2015 ; Rodriguez-Cueto et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Key Disease Mechanisms Linked to Amyotrophic Lateral Sclerosis in Spinal Cord Motor Neurons

Bottero

Santiago²,

Quinn³

et al. 2022

Front. Mol. Neurosci.

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no modifying treatments available. The molecular mechanisms underpinning disease pathogenesis are not fully understood. Recent studies have employed co-expression networks to identify key genes, known as “switch genes”, responsible for dramatic transcriptional changes in the blood of ALS patients. In this study, we directly investigate the root cause of ALS by examining the changes in gene expression in motor neurons that degenerate in patients. Co-expression networks identified in ALS patients’ spinal cord motor neurons revealed 610 switch genes in seven independent microarrays. Switch genes were enriched in several pathways, including viral carcinogenesis, PI3K-Akt, focal adhesion, proteoglycans in cancer, colorectal cancer, and thyroid hormone signaling. Transcription factors ELK1 and GATA2 were identified as key master regulators of the switch genes. Protein-chemical network analysis identified valproic acid, cyclosporine, estradiol, acetaminophen, quercetin, and carbamazepine as potential therapeutics for ALS. Furthermore, the chemical analysis identified metals and organic compounds including, arsenic, copper, nickel, and benzo(a)pyrene as possible mediators of neurodegeneration. The identification of switch genes provides insights into previously unknown biological pathways associated with ALS.

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“…The best known endogenous agonists of PPARγ are fatty acids such as 15-deoxy-∆ 12,14 prostaglandin (PG) J2 (15d-PGJ 2 ), 15-hydroxyeicosatetraenoic acid (15-HETE), 9-or 13-hydroxyoctadecadienoic acid (9/13-HODE), all derived from oxidation cascades of poly-unsaturated fatty acids (PUFA) as linoleic acid or arachidonic acid [21,22]. Other natural PPARγ agonists are the phospholipids lysophosphatidic acid and hexadecylazelaoyl phosphatidylcholine, nitroalkenes and some dietary lipids such as isoflavones and flavonoids [23]. Recent studies have disclosed that astragaladoside IV from herbal extract [24], alliin from garlic [25] or cannabidiol from cannabis [26] were PPARγ agonists.…”

Section: Pparγ Molecular Leversmentioning

confidence: 99%

“…Recent studies have disclosed that astragaladoside IV from herbal extract [24], alliin from garlic [25] or cannabidiol from cannabis [26] were PPARγ agonists. Synthetic PPARγ agonists are thiazolidinediones (TZDs, e.g., rosiglita-zone, pioglitazone, troglitazone) which share as common structural motifs a cyclic tail, an aromatic core, and an acidic head [23]. Noteworthy, the ability of TZDs to cross the brain blood barrier is controversial [6] and some receptor-independent effects of TZDs treatment have been reported [6,22].…”

Section: Pparγ Molecular Leversmentioning

confidence: 99%

PPAR Gamma and Viral Infections of the Brain

Layrolle

Payoux

Chavanas

2021

IJMS

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Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a master regulator of metabolism, adipogenesis, inflammation and cell cycle, and it has been extensively studied in the brain in relation to inflammation or neurodegeneration. Little is known however about its role in viral infections of the brain parenchyma, although they represent the most frequent cause of encephalitis and are a major threat for the developing brain. Specific to viral infections is the ability to subvert signaling pathways of the host cell to ensure virus replication and spreading, as deleterious as the consequences may be for the host. In this respect, the pleiotropic role of PPARγ makes it a critical target of infection. This review aims to provide an update on the role of PPARγ in viral infections of the brain. Recent studies have highlighted the involvement of PPARγ in brain or neural cells infected by immunodeficiency virus 1, Zika virus, or human cytomegalovirus. They have provided a better understanding on PPARγ functions in the infected brain, and revealed that it can be a double-edged sword with respect to inflammation, viral replication, or neuronogenesis. They unraveled new roles of PPARγ in health and disease and could possibly help designing new therapeutic strategies.

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Minutes of PPAR-γ agonism and neuroprotection

Cited by 39 publications

References 91 publications

Antidepressant‐like effect of rosmarinic acid during LPS‐induced neuroinflammatory model: The potential role of cannabinoid receptors/PPAR‐γ signaling pathway

Antidepressant‐like effect of rosmarinic acid during LPS‐induced neuroinflammatory model: The potential role of cannabinoid receptors/PPAR‐γ signaling pathway

Key Disease Mechanisms Linked to Amyotrophic Lateral Sclerosis in Spinal Cord Motor Neurons

PPAR Gamma and Viral Infections of the Brain

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