TLR/mTOR inflammatory signaling pathway: novel insight for the treatment of schizophrenia.

The Toll-like receptor (TLR)/mammalian target of rapamycin (mTOR) signaling pathway is involved in the intracellular regulation of protein synthesis, specifically the ones that mediate neuronal morphology and facilitate synaptic plasticity. The activity of TLR/mTOR signaling has been disrupted, leading to neurodevelopment and deficient synaptic plasticity, which are the main symptoms of schizophrenia. The TLR receptor activates the mTOR signaling pathway and increases the elevation of inflammatory cytokines. Interleukin (IL)-6 is the most commonly altered cytokine, while IL-1, tumor necrosis factor, and interferon (IFN) also lead to SCZ. Anti-inflammatory and anti-oxidative agents such as celecoxib, aspirin, minocycline, and omega-3 fatty acids have shown efficiency against SCZ. As a result, inhibition of the inflammatory process could be suggested for the treatment of SCZ. So mTOR/TLR blockers represent the treatment of SCZ due to their inflammatory consequences. The objective of the present work was to find a novel anti-inflammatory agent that may block the mTOR/TLR inflammatory signaling pathways and might pave the way for the treatment of neuroinflammatory SCZ. Data were collected from experimental and clinical studies published in English between 1998 and October 2022 from Google Scholar, PubMed, Scopus, and the Cochrane library.

Impact of curcumin on p38 MAPK: therapeutic implications.

Curcumin (diferuloylmethane) is a herbal remedy which possesses numerous biological attributes including anti-inflammatory, anti-oxidant and anti-cancer properties. Curcumin has been shown to impact a number of signaling pathways including nuclear factor kappa B (NF-KB), reactive oxygen species (ROS), Wingless/Integrated (Wnt), Janus kinase-signal transducer and activator of mitogen-activated protein kinase (MAPK) and transcription (JAK/STAT). P38 belongs to the MAPKs, is known as a stress-activated MAPK and is involved in diverse biological responses. P38 is activated in various signaling cascades. P38 plays a role in inflammation, cell differentiation, proliferation, motility and survival. This cascade can serve as a therapeutic target in many disorders. Extensive evidence confirms that curcumin impacts the P38 MAPK signaling pathway, through which it exerts anti-inflammatory, neuroprotective, and apoptotic effects. Hence, curcumin can positively affect inflammatory disorders and cancers, as well as to increase glucose uptake in cells. This review discusses the pharmacological and therapeutic effects of curcumin as effected through p38 MAPK.

BDNF-TrkB Signaling Pathway in Spinal Cord Injury: Insights and Implications.

Spinal cord injury (SCI) is a neurodegenerative disorder that has critical impact on patient's life expectance and life span, and this disorder also leads to negative socioeconomic features. SCI is defined as a firm collision to the spinal cord which leads to the fracture and the dislocation of vertebrae. The current available treatment is surgery. However, it cannot fully treat SCI, and many consequences remain after the surgery. Accordingly, finding new therapeutics is critical. BDNF-TrkB signaling is a vital signaling in neuronal differentiation, survival, overgrowth, synaptic plasticity, etc. Hence, many studies evaluate its impact on various neurodegenerative disorders. There are several studies evaluating this signaling in SCI, and they show promising outcomes. It was shown that various exercises, chemical interventions, etc. had significant positive impact on SCI by affecting BDNF-TrkB signaling pathway. This study aims to accumulate and evaluate these data and inspect whether this signaling is effective or not.

LRRK2; Communicative Role in the Treatment of Parkinson's Disease and Ulcerative Colitis Overlapping.

BACKGROUND: Involvement of gastrointestinal inflammation in Parkinson's disease (PD) pathogenesis and movement have progressively emerged. Inflammation is involved in the etiology of both PD and inflammatory bowel disease (IBD). Transformations in leucine-rich recurrent kinase 2 (LRRK2) are among the best hereditary supporters of IBD and PD. Elevated levels of LRRK2 have been reported in stimulated colonic tissue from IBD patients and peripheral invulnerable cells from irregular PD patients; thus, it is thought that LRRK2 directs inflammatory cycles. OBJECTIVE: Since its revelation, LRRK2 has been seriously linked in neurons, albeit various lines of proof affirmed that LRRK2 is profoundly communicated in invulnerable cells. Subsequently, LRRK2 might sit at a junction by which stomach inflammation and higher LRRK2 levels in IBD might be a biomarker of expanded risk for inconsistent PD or potentially may address a manageable helpful objective in incendiary sicknesses that increment the risk of PD. Here, we discuss how PD and IBD share covering aggregates, especially regarding LRRK2 and present inhibitors, which could be a helpful objective in ongoing treatments. METHOD: English data were obtained from Google Scholar, PubMed, Scopus, and Cochrane library studies published between 1990-December 2022. RESULT: Inhibitors of the LRRK2 pathway can be considered as the novel treatment approaches for IBD and PD treatment. CONCLUSION: Common mediators and pathways are involved in the pathophysiology of IBD and PD, which are majorly correlated with inflammatory situations. Such diseases could be used for further clinical investigations.

Sodium Glucose Transporter-2 Inhibitors (SGLT2Is)-TLRs Axis Modulates Diabetes.

Diabetes affects millions of people worldwide and is mainly associated with impaired insulin function. To date, various oral anti-diabetic drugs have been developed, of which, the sodium glucose transporter-2 inhibitors (SGLT2Is) are of the most recent classes that have been introduced. They differ from other classes in terms of their novel mechanism of actions and unique beneficial effects rather than just lowering glucose levels. SGLT2Is can protect body against cardiovascular events and kidney diseases even in non-diabetic individuals. SGLT2Is participate in immune cell activation, oxidative stress reduction, and inflammation mediation, thereby, moderating diabetic complications. In addition, toll like receptors (TLRs) are the intermediators of the immune system and inflammatory process, thus it's believed to play crucial roles in diabetic complications, particularly the ones that are related to inflammatory reactions. SGLT2Is are also effective against diabetic complications via their anti-inflammatory and oxidative properties. Given the anti-inflammatory properties of TLRs and SGLT2Is, this review investigates how SGLT2Is can affect the TLR pathway, and whether this could be favorable toward diabetes.