Neuroprotective effects of gemfibrozil in neurological disorders: Focus on inflammation and molecular mechanisms

Abstract

BackgroundGemfibrozil (Gem) is a drug that has been shown to activate PPAR‐α, a nuclear receptor that plays a key role in regulating lipid metabolism. Gem is used to lower the levels of triglycerides and reduce the risk of coronary heart disease in patients. Experimental studies in vitro and in vivo have shown that Gem can prevent or slow the progression of neurological disorders (NDs), including cerebral ischemia (CI), Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Neuroinflammation is known to play a significant role in these disorders.MethodThe literature review for this study was conducted by searching Scopus, Science Direct, PubMed, and Google Scholar databases.ResultThe results of this study show that Gem has neuroprotective effects through several cellular and molecular mechanisms such as: (1) Gem has the ability to upregulate pro‐survival factors (PGC‐1α and TFAM), promoting the survival and function of mitochondria in the brain, (2) Gem strongly inhibits the activation of NF‐κB, AP‐1, and C/EBPβ in cytokine‐stimulated astroglial cells, which are known to increase the expression of iNOS and the production of NO in response to proinflammatory cytokines, (3) Gem protects dopamine neurons in the MPTP mouse model of PD by increasing the expression of PPARα, which in turn stimulates the production of GDNF in astrocytes, (4) Gem reduces amyloid plaque pathology, reduces the activity of glial cells, and improves memory, (5) Gem increases myelin genes expression (MBP and CNPase) via PPAR‐β, and (6) Gem increases hippocampal BDNF to counteract depression.ConclusionAccording to the study, Gem was investigated for its potential therapeutic effect in NDs. Further research is needed to fully understand the therapeutic potential of Gem in NDs.

Caffeic acid phenethyl ester inhibits neuro-inflammation and oxidative stress following spinal cord injury by mitigating mitochondrial dysfunction via the SIRT1/PGC1α/DRP1 signaling pathway

“…At its core, SIRT1, a NAD + -dependent deacetylase belonging to the sirtuin family, exerts its influence by removing acetyl groups from specific target proteins, thereby regulating their activity [ 51 , 52 ]. PGC1α is a transcriptional coactivator with the ability to modulate the expression of genes responsible for mitochondrial biogenesis, oxidative phosphorylation, and gluconeogenesis [ 53 – 55 ]. The functional synergy of the SIRT1/PGC1α pathway is evident in that SIRT1 activates PGC1α through deacetylation, leading to heightened PGC1α activity [ 56 ].…”

Neuron-type specific aging-rate reveals age decelerating interventions preventing neurodegeneration

“…The top anti-NeuronAge compound hits contain several (9 out of 16) for which a protective effect for neurons has been previously documented, thus validating our approach (Figure 6B). The glycogen synthase kinase 3 (GSK3) inhibitor AR-A014418 was shown to inhibit beta-amyloid induced neurodegeneration 38 ; the selective serotonin reuptake inhibitor uoxetine protects against neurotoxicity and neurodegeneration [39][40][41] ; the PPAR-alpha activator gem brozil exhibits neuroprotective effects via upregulating pro-survival factors and suppressing in ammation 42 ; the kinase inhibitor sorafenib protects against neurodegeneration in C. elegans 43 ; the selective aryl hydrocarbon receptor modulator 3,3'diindolylmethane (DIM) is neuroprotective and promotes brain-derived neurotrophic factor (BDNF) 44,45 ;…”

Special Issue “Neurogenetics in Neurology”

“…Bioinformatic analysis and experimental indication recommend that miR-30c controls many genes as targets that are linked with several pathogenic processes, such as autophagy, apoptosis, ER stress, inflammation, oxidative stress, thrombosis, and neurovascular function, thus contributing to the pathophysiology of diverse neurological diseases. In this context, the therapeutic targeting of miR-30c via synthetic mimics or inhibitors is under evaluation [8][9][10].…”