trka

Neural differentiation is triggered by the activation of multiple signaling pathways initiated by various neurotrophic factors. An elucidation of these mechanisms is anticipated to facilitate the prevention of diseases and the development of novel therapeutic approaches. Alternative small-molecule inducers for neuroscience studies are required instead of protein-based reagents for more efficient and convenient experiments. We demonstrated that small molecules of thieno[2,3-b]pyridine derivatives that induce neural differentiation, compounds 3a and 9a in particular, exhibited significant neuritogenic activity in rat pheochromocytoma (PC12) cells...

Proton FO F1 -ATPase is the key enzyme in E. coli under fermentative conditions. In this study the role of E. coli proton ATPase in the μ and formation of metabolic pathways during the fermentation of mixture of glucose, glycerol and formate using the DK8 (lacking FO F1 ) mutant strain was investigated. It was shown that the contribution of FO F1 -ATPase in the specific growth rate was ~45 %. Formate was not taken up in the DK8 strain during the initial hours of the growth. The utilization rates of glucose and glycerol were unchanged in DK8, however, the production of succinate, lactate and ethanol was decreased causing a reduction of the redox state up to -450 mV...

The appropriate and specific response of nerve cells to various external cues is essential for the establishment and maintenance of neural circuits, and this process requires the proper recruitment of adaptor molecules to selectively activate downstream pathways. Here, we identified that DOK6, a member of the Dok (downstream of tyrosine kinases) family, is required for the maintenance of peripheral axons, and that loss of Dok6 can cause typical peripheral neuropathy symptoms in mice, manifested as impaired sensory, abnormal posture, paw deformities, blocked nerve conduction, and dysmyelination...

Nerve growth factor (NGF) and its receptor, tropomyosin receptor kinase A (TrkA), are known to play important roles in the immune and nervous system. However, the effects of NGF on the osteogenic differentiation of dental pulp stem cells (DPSCs) remain unclear. This study aimed to investigate the role of NGF on the osteogenic differentiation of DPSCs in vitro and the underlying mechanisms. DPSCs were cultured in osteogenic differentiation medium containing NGF (50 ng/mL) for 7 days. Then osteogenic-related genes and protein markers were analysed using qRT-PCR and Western blot, respectively...

A feature of peripheral artery diseases (PAD) includes limb ischemia/reperfusion (I/R) and ischemia. Both I/R and ischemia amplify muscle afferent nerve-activated reflex sympathetic nervous and blood pressure responses (termed as exercise pressor reflex). Nevertheless, the underlying mechanisms responsible for the exaggerated autonomic responses in PAD are undetermined. Previous studies suggest that acid-sensing ion channels (ASICs) in muscle dorsal root ganglion (DRG) play a leading role in regulating the exercise pressor reflex in PAD...

Repotrectinib (AUGTYRO™) is a next-generation, oral, small-molecule kinase inhibitor of proto-oncogene tyrosine-protein kinase ROS1 (ROS1) and tropomyosin receptor tyrosine kinases (TRKs) TRKA, TRKB, and TRKC. It is being developed by Turning Point Therapeutics, a wholly owned subsidiary of Bristol-Myers Squibb (BMS), for the treatment of locally advanced or metastatic solid tumours, including non-small cell lung cancer (NSCLC). Repotrectinib is a next-generation tyrosine kinase inhibitor rationally designed to inhibit ROS1 and TRK fusion, including in the presence of resistance mutations such as solvent-front mutations...

OBJECTIVES: To assess the role of CCL19+ lymph node stromal cells of the joint draining popliteal lymph node (pLN) for the development of arthritis. METHODS: CCL19+ lymph node stromal cells were spatiotemporally depleted for 5 days in the pLN before the onset of collagen-induced arthritis (CIA) using Ccl19-Cre x iDTR mice. In addition, therapeutic treatment with recombinant CCL19-IgG, locally injected in the footpad, was used to confirm the results. RNA sequencing of lymph node stromal cells combined with T cell co-culture assays using tropomyosin receptor kinase (Trk) family inhibitors together with in vivo local pLN siRNA treatments were used to elucidate the pathway by which CCL19+ lymph node stromal cells initiate the onset of arthritis...

PC12 cells, which are derived from rat adrenal pheochromocytoma cells, are widely used for the study of neuronal differentiation. NGF induces neuronal differentiation in PC12 cells by activating intracellular pathways via the TrkA receptor, which results in elongated neurites and neuron-like characteristics. Moreover, the differentiation requires both the ERK1/2 and p38 MAPK pathways. In addition to NGF, BMPs can also induce neuronal differentiation in PC12 cells. BMPs are part of the TGF-β cytokine superfamily and activate signaling pathways such as p38 MAPK and Smad...

The progressive worsening of disc degeneration and related nonspecific back pain are prominent clinical issues that cause a tremendous economic burden. Activation of reactive oxygen species (ROS) related inflammation is a primary pathophysiologic change in degenerative disc lesions. This pathological state is associated with M1 macrophages, apoptosis of nucleus pulposus cells (NPC), and the ingrowth of pain-related sensory nerves. To address the pathological issues of disc degeneration and discogenic pain, we developed MnO2 @TMNP, a nanomaterial that encapsulated MnO2 nanoparticles with a TrkA-overexpressed macrophage cell membrane (TMNP)...

OBJECTIVE: To observe the effects of electroacupuncture at Neiguan (PC6) at different time points on reperfusion arrhythmia (RA) after myocardial ischemia and reperfusion in rats, and to investigate the correlation of this protective effect with nerve growth factor (NGF), tyrosine kinase A (TrkA), tyrosine hydroxylase (TH), and norepinephrine (NE). METHODS：A total of 72 Sprague-Dawley male rats were randomly divided into six groups ( n = 12 rats/group): normal group (Norm), sham operation group (Sham), ischemia reperfusion group (I/R), pre-ischemic electroacupuncture group (EAI), pre-reperfusion electroacupuncture group (EAII), post-reperfusion electroacupuncture group (EAIII)...

Recent findings highlight myelin breakdown as a decisive early event in Alzheimer's Disease (AD) acting as aggravating factor of its progression. However, it is still unclear whether myelin loss is attributed to increased oligodendrocyte vulnerability, reduced repairing capacity or toxic stimuli. In the present study, we sought to clarify the starting point of myelin disruption accompanied with Oligodendrocyte Progenitor Cell (OPC) elimination in the brain of the 5xFAD mouse model of AD at 6 months of age in Dentate Gyrus of the hippocampus in relation to neurotrophin system...

N-acetylcysteine (NAC), a mucolytic agent and an antidote to acetaminophen intoxication, has been studied in experimental conditions and trials exploring its analgesic activity based on its antioxidant and anti-inflammatory properties. The purpose of this study is to investigate additional mechanisms, namely, the inhibition of nerve growth factor (NGF) and the activation of the Tropomyosin receptor kinase A (TrkA) receptor, which is responsible for nociception. In silico studies were conducted to evaluate dithiothreitol and NAC's interaction with TrkA...

BACKGROUND: As a novel necrosis manner, ferroptosis has been increasingly reported to play a role in tumor progression and treatment, however, the specific mechanisms underlying its development in prostate cancer remain unclear. Growing evidence showed that peroxisome plays a key role in ferroptosis. Herein, we identified a novel mechanism for the involvement of ferroptosis in prostate cancer progression, which may provide a new strategy for clinical treatment of prostate cancer. METHODS: Label-Free Mass spectrometry was used to screen and identify candidate proteins after ferroptosis inducer-ML210 treatment...

Melanoma cells, deriving from neuroectodermal melanocytes, may exploit the nervous system's immune privilege for growth. Here we show that nerve growth factor (NGF) has both melanoma cell intrinsic and extrinsic immunosuppressive functions. Autocrine NGF engages tropomyosin receptor kinase A (TrkA) on melanoma cells to desensitize interferon γ signaling, leading to T and natural killer cell exclusion. In effector T cells that upregulate surface TrkA expression upon T cell receptor activation, paracrine NGF dampens T cell receptor signaling and effector function...

Gastrointestinal stromal tumors (GISTs) are typically characterized by activating mutations of the KIT proto-oncogene receptor tyrosine kinase (KIT) or platelet-derived growth factor receptor alpha (PDGFRA). Recently, the neurotrophic tyrosine receptor kinase (NTRK) fusion was reported in a small subset of wild-type GIST. We examined trk IHC and NTRK gene expressions in GIST. Pan-trk immunohistochemistry (IHC) was positive in 25 (all 16 duodenal and 9 out of 16 small intestinal GISTs) of 139 cases, and all pan-trk positive cases showed diffuse and strong expression of c-kit...

Current hypotheses on the mechanisms underlying the development and plasticity of the ocular dominance system through competitive interactions between pathways serving the two eyes strongly suggest the involvement of neurotrophins and their high affinity receptors. In the cat, infusion of the tyrosine kinase B ligand (trkB), neurotrophin-4/5 (NT-4/5), abolishes ocular dominance plasticity that follows monocular deprivation (Gillespie et al., 2000), while tyrosine kinase A and C ligands (trkA and trkC) do not have this effect...

Brachial plexus root avulsion (BPRA) injury arises from challenging delivery during childbirth, sports-related incidents, or car accidents, leading to extensive loss of motor neurons (MNs) and subsequent paralysis, including both motor and sensory impairment. Surgical nerve re-implantation cannot effectively restore motor function, and the survival of injured MNs is vital for axon regeneration and re-innervating the target muscles. Therefore, identifying novel molecular targets to improve injured MNs survival is of great significance in the treatment of BPRA injuries...

BACKGROUND: Alzheimer's disease (AD) is a multifaceted neurological ailment affecting more than 50 million individuals globally, distinguished by a deterioration in memory and cognitive abilities. Investigating neurotrophin growth factors could offer significant contributions to understanding AD progression and prospective therapeutic interventions. METHODS AND RESULTS: The present investigation collected blood samples from 50 patients diagnosed with AD and 50 healthy individuals serving as controls...

The pathogenesis of multiple sclerosis (MS) suggests that, in genetically susceptible subjects, T lymphocytes undergo activation in the peripheral compartment, pass through the BBB, and cause damage in the CNS. They produce pro-inflammatory cytokines; induce cytotoxic activities in microglia and astrocytes with the accumulation of reactive oxygen species, reactive nitrogen species, and other highly reactive radicals; activate B cells and macrophages and stimulate the complement system. Inflammation and neurodegeneration are involved from the very beginning of the disease...

Nerve growth factor (NGF) signalling affects spermatogenesis and mature sperm traits. In this paper, we aimed to evaluate the distribution and the role of NGF and its receptors (p75NTR and TrKA) on the reproductive apparatus (testis and epididymis) and sperm of fertile men (F) and men with different pathologies, namely varicocele (V) and urogenital infections (UGIs). We collected semen samples from 21 individuals (31-40 years old) subdivided as follows: V ( n = 7), UGIs ( n = 7), and F ( n = 7). We submitted the semen samples to bacteriological analysis, leucocyte identification, and analysis of sperm parameters (concentration, motility, morphology, and viability)...