许多途径可以导致从健康表型到患病表型的转变。然而,没有那么多相反方向的路线;也就是说,治疗不同的疾病。因此,以下紧迫的问题仍然存在:什么是致病途径,以及如何为治疗目的抵消它们?人类细胞含有>500个蛋白激酶和近200个蛋白磷酸酶,作用于数千种蛋白质,包括细胞生长因子。我们在这里讨论具有致病或代谢能力的神经营养蛋白,特别是脑源性神经营养因子(BDNF),神经生长因子(NGF),pro-NGF,神经营养蛋白-3(NT-3),和它们的受体Trk(酪氨酸受体激酶;发音为“track”)。的确,我们介绍了trackins这个词,代表Trk靶向药物,在TrkBBDNF的功能中起激动或拮抗作用,TrkCNT-3,TrkANGF,和TrkApro-NGF受体。根据我们自己发表的结果,在其他作者的支持下,我们的目标是更新和扩大我们的跟踪概念,专注于(1)激动Trackins作为(1a)神经营养因子缺乏心脏代谢紊乱(高血压,动脉粥样硬化,2型糖尿病,代谢综合征,肥胖,糖尿病性勃起功能障碍和心房颤动)和(1b)神经退行性疾病(阿尔茨海默病,帕金森病,和多发性硬化症),和(2)拮抗轨道,特别是前列腺癌和乳腺癌的TrkANGF抑制剂,疼痛,和致心律失常性右心室发育不良.总之,TrkANGF的可药用性,TrkApro-NGF,TrkBBDNF,和TrkCNT-3受体通过trackin需要进一步的翻译追求。这可以为我们的患者提供奖励。
Many routes may lead to the transition from a healthy to a diseased phenotype. However, there are not so many routes to travel in the opposite direction; that is, therapy for different diseases. The following pressing question thus remains: what are the pathogenic routes and how can be they counteracted for therapeutic purposes? Human cells contain >500 protein kinases and nearly 200 protein phosphatases, acting on thousands of proteins, including cell growth factors. We herein discuss neurotrophins with pathogenic or metabotrophic abilities, particularly brain-derived neurotrophic factor (BDNF), nerve growth factor (
NGF), pro-
NGF, neurotrophin-3 (NT-3), and their receptor Trk (tyrosine receptor kinase; pronounced \"track\"). Indeed, we introduced the word trackins, standing for Trk-targeting drugs, that play an agonistic or antagonistic role in the function of TrkBBDNF, TrkCNT-3, TrkANGF, and TrkApro-
NGF receptors. Based on our own published results, supported by those of other authors, we aim to update and enlarge our trackins concept, focusing on (1) agonistic trackins as possible drugs for (1a) neurotrophin-deficiency cardiometabolic disorders (hypertension, atherosclerosis, type 2 diabetes mellitus, metabolic syndrome, obesity, diabetic erectile dysfunction and atrial fibrillation) and (1b) neurodegenerative diseases (Alzheimer\'s disease, Parkinson\'s disease, and multiple sclerosis), and (2) antagonistic trackins, particularly TrkANGF inhibitors for prostate and breast cancer, pain, and arrhythmogenic right-ventricular dysplasia. Altogether, the druggability of TrkANGF, TrkApro-
NGF, TrkBBDNF, and TrkCNT-3 receptors via trackins requires a further translational pursuit. This could provide rewards for our patients.