TRP (transient receptor potential) ion channel family: structures, biological functions and therapeutic interventions for diseases

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: July 5, 2023

Abstract Transient receptor potential (TRP) channels are sensors for a variety of cellular and environmental signals. Mammals express total 28 different TRP channel proteins, which can be divided into seven subfamilies based on amino acid sequence homology: TRPA (Ankyrin), TRPC (Canonical), TRPM (Melastatin), TRPML (Mucolipin), TRPN (NO-mechano-potential, NOMP), TRPP (Polycystin), TRPV (Vanilloid). They class ion found in numerous tissues cell types permeable to wide range cations such as Ca 2+ , Mg Na + K others. responsible various sensory responses including heat, cold, pain, stress, vision taste activated by number stimuli. Their predominantly location the surface, their interaction with physiological signaling pathways, unique crystal structure make TRPs attractive drug targets implicate them treatment diseases. Here, we review history discovery, summarize structures functions family, highlight current understanding role pathogenesis human disease. Most importantly, describe channel-related therapeutic interventions diseases limitations targeting clinical applications.

Language: Английский

---

Targeting PI3K/AKT signaling pathway in obesity

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 159, P. 114244 - 114244

Published: Jan. 11, 2023

Obesity is a disorder with an increasing prevalence, which impairs the life quality of patients and intensifies societal health care costs. The development safe innovative prevention strategies therapeutic approaches thus great importance. complex pathophysiology obesity involves multiple signaling pathways that influence energy metabolism in different tissues. phosphatidylinositol 3-kinases (PI3K)/protein kinase B (AKT) pathway critical for metabolic homeostasis its function insulin-sensitive tissues described context health, obesity-related complications. PI3K family participates regulation diverse physiological processes including but not limited to cell growth, survival, differentiation, autophagy, chemotaxis, depending on cellular context. AKT downstream insulin pathway, promotes by targeting plethora regulatory proteins control glucose lipid metabolism. Natural products are essential treatment many human diseases, obesity. Anti-obesity natural compounds effect pathophysiological mechanisms involved development. Numerous recent preclinical studies reveal advances using plant secondary metabolites target PI3K/AKT management. In this paper druggability as anti-obesity potential evaluated. Perspectives limitations clinical implementation management modulating suggested.

Language: Английский

---

Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 14, 2023

Abstract The ageing process is a systemic decline from cellular dysfunction to organ degeneration, with more predisposition deteriorated disorders. Rejuvenation refers giving aged cells or organisms youthful characteristics through various techniques, such as reprogramming and epigenetic regulation. great leaps in rejuvenation prove that not one-way street, many rejuvenative interventions have emerged delay even reverse the process. Defining mechanism by which roadblocks signaling inputs influence complex programs essential for understanding developing strategies. Here, we discuss intrinsic extrinsic factors counteract cell rejuvenation, targeted core mechanisms involved this Then, critically summarize latest advances state-of-art strategies of rejuvenation. Various methods also provide insights treating specific ageing-related diseases, including reprogramming, removal senescence (SCs) suppression senescence-associated secretory phenotype (SASP), metabolic manipulation, stem cells-associated therapy, dietary restriction, immune heterochronic transplantation, etc. potential applications therapy extend cancer treatment. Finally, analyze detail therapeutic opportunities challenges technology. Deciphering will further into anti-ageing disease treatment clinical settings.

Language: Английский

---

Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 1, 2024

Abstract Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family (PGC-1s), consisting of three members encompassing PGC-1α, PGC-1β, and PGC-1-related coactivator (PRC), was discovered more than a quarter-century ago. PGC-1s are essential coordinators many vital cellular events, including mitochondrial functions, oxidative stress, endoplasmic reticulum homeostasis, inflammation. Accumulating evidence has shown that implicated in diseases, such as cancers, cardiac diseases cardiovascular neurological disorders, kidney motor system metabolic disorders. Examining the upstream modulators co-activated partners identifying critical biological events modulated by downstream effectors contribute to presentation elaborate network PGC-1s. Furthermore, discussing correlation between well summarizing therapy targeting helps make individualized precise intervention methods. In this review, we summarize basic knowledge regarding molecular regulatory network, discuss physio-pathological roles human review application PGC-1s, diagnostic prognostic value several therapies pre-clinical studies, suggest directions for future investigations. This presents immense potential treatment hopefully facilitates promotion new therapeutic targets.

Language: Английский

---

Astrocytic LRP1 enables mitochondria transfer to neurons and mitigates brain ischemic stroke by suppressing ARF1 lactylation

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(9), P. 2054 - 2068.e14

Published: June 20, 2024

Language: Английский

---

Inflammation in diabetes complications: molecular mechanisms and therapeutic interventions

MedComm, Journal Year: 2024, Volume and Issue: 5(4)

Published: April 1, 2024

Abstract At present, diabetes mellitus (DM) has been one of the most endangering healthy diseases. Current therapies contain controlling high blood sugar, reducing risk factors like obesity, hypertension, and so on; however, DM patients inevitably eventually progress into different types complications, resulting in poor quality life. Unfortunately, clear etiology pathogenesis complications have not elucidated owing to intricate whole‐body systems. The immune system was responsible regulate homeostasis by triggering or resolving inflammatory response, indicating it may be necessary complications. In fact, previous studies shown inflammation plays multifunctional roles is attracting attention meaningful therapeutic strategy. To this end, review systematically concluded current over relationships susceptible (e.g., diabetic cardiomyopathy, retinopathy, peripheral neuropathy, nephropathy) inflammation, ranging from cell cytokines interaction pathomechanism organ injury. Besides, we also summarized various strategies improve target special remedies conventional lifestyle changes. This will offer a panoramic insight mechanisms an perspective discuss contemporary clinical interventions.

Language: Английский

---

Cytokines as Key Players in Obesity Low Grade Inflammation and Related Complications

Obesity Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 100585 - 100585

Published: Jan. 1, 2025

Language: Английский

---

Therapeutic targeting of obesity-induced neuroinflammation and neurodegeneration

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 17, 2025

Obesity is a major modifiable risk factor leading to neuroinflammation and neurodegeneration. Excessive fat storage in obesity promotes the progressive infiltration of immune cells into adipose tissue, resulting release pro-inflammatory factors such as cytokines adipokines. These inflammatory mediators circulate through bloodstream, propagating inflammation both periphery central nervous system. Gut dysbiosis, which results leaky intestinal barrier, exacerbates plays significant role linking pathogenesis neurodegeneration gut-brain/gut-brain-liver axis. Inflammatory states within brain can lead insulin resistance, mitochondrial dysfunction, autolysosomal increased oxidative stress. disruptions impair normal neuronal function subsequently cognitive decline motor deficits, similar pathologies observed neurodegenerative diseases, including Alzheimer's disease, multiple sclerosis, Parkinson's disease. Understanding underlying disease mechanisms crucial for developing therapeutic strategies address defects these metabolic pathways. In this review, we summarize provide insights different strategies, methods alter gut lifestyle changes, dietary supplementation, well pharmacological agents derived from natural sources, that target obesity-induced

Language: Английский

---

Effects of combined aerobic exercise and diet on cardiometabolic health in patients with obesity and type 2 diabetes: a systematic review and meta-analysis

BMC Sports Science Medicine and Rehabilitation, Journal Year: 2023, Volume and Issue: 15(1)

Published: Dec. 4, 2023

Lifestyle modifications involving diet and exercise are recommended for patients diagnosed with obesity type 2 diabetes mellitus (T2DM). The purpose of this review was to systematically evaluate the effects combined aerobic (AEDT) on various cardiometabolic health-related indicators among individuals T2DM.A comprehensive search PubMed/Medline, Web Science, Scopus, Science Direct, Cochrane, Google Scholar databases conducted meta-analysis. Cochrane risk bias tool used eligible studies, GRADE rate certainty evidence. A random-effects model continuous variables used, results were presented as mean differences or standardised 95% confidence intervals.A total 16,129 studies retrieved; 20 included, data extracted from 1,192 participants. findings revealed significant improvements in body mass index, weight, waist circumference, systolic blood pressure, diastolic cholesterol, triglycerides, fasting glucose, plasma insulin, glycated hemoglobin, leptin, interleukin-6, C-reactive protein, adiponectin (p < 0.05) compared standard treatment (ST) group. No observed between AEDT ST groups fat mass, hip waist-to-hip ratio, high-density lipoprotein low-density tumor necrosis factor-alpha. present based low- moderate-quality evidence.AEDT may be a critical behavior holistic benefits contemporary anti-obesity medication due its positive impact T2DM. Nevertheless, further robust evidence is necessary determine whether an effective intervention lowering cardiovascular metabolic factors

Language: Английский

---

A narrative review of approved and emerging anti-obesity medications

Saudi Pharmaceutical Journal, Journal Year: 2023, Volume and Issue: 31(10), P. 101757 - 101757

Published: Aug. 24, 2023

Recently, many drugs have been approved for halting overweight and obesity-few types of research shifted to using Anti-obesity medications (AOM) solely well-being shape-keeping.

Language: Английский

---