Trk受体在脑部疾病与功能紊乱中的复杂关系
The Intricate Relationship of Trk Receptors in Brain Diseases and Disorders.
作者信息
Dahiya Sarthak, Sharma Poonam, Sharma Bhupesh, Saroj Priyanka, Kharkwal Harsha, Sharma Nitin
机构信息
Department of Pharmacology, Amity Institute of Pharmacy, Amity University Uttar Pradesh, Noida, Uttar Pradesh, India.
Lloyd Institute of Management and Technology, Plot No.-11, Knowledge Park-II, Greater Noida, Uttar Pradesh, 201306, India.
出版信息
Mol Neurobiol. 2025 May 23. doi: 10.1007/s12035-025-05058-2.
The tropomyosin-related tyrosine kinases or neurotrophic tyrosine kinase receptors are a group of tyrosine kinases that play a crucial role in regulating neuronal growth and development. Neurotrophins are a class of protein-secreting cells that serve as the primary ligand for the Trk receptors. The four primary neurotrophins are nerve growth factor (NGF), brain-derived nerve factor (BDNF), neurotrophin-3, and neurotrophin-4/5. Mounting evidence suggests that Trk receptors can be categorized into three types: TrkA, TrkB, and TrkC. These receptors play a crucial role in facilitating neuronal growth and development. Trk receptors influence the survival and differentiation of neurons via many signalling cascades. Neurotrophin interaction with Trk receptors triggers a signalling cascade involving PLC, PI3K/Akt, and Ras/MAPK signalling pathways. Emerging evidence suggests that diminished neurotrophic support, changes in Trk receptor expression, or disruptions in signalling cascades play a crucial role in the development of various neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), autism spectrum disorder (ASD), and many more. This review specifically explores therapeutic approaches targeting Trk receptors, their ligands, and Trk signaling in the context of various brain disorders. We focus on the potential for modulating or inhibiting Trk receptors as a treatment strategy for brain diseases.
原肌球蛋白相关酪氨酸激酶或神经营养性酪氨酸激酶受体是一组在调节神经元生长和发育中起关键作用的酪氨酸激酶。神经营养因子是一类分泌蛋白质的细胞,作为Trk受体的主要配体。四种主要的神经营养因子是神经生长因子(NGF)、脑源性神经因子(BDNF)、神经营养因子-3和神经营养因子-4/5。越来越多的证据表明,Trk受体可分为三种类型:TrkA、TrkB和TrkC。这些受体在促进神经元生长和发育中起关键作用。Trk受体通过许多信号级联反应影响神经元的存活和分化。神经营养因子与Trk受体的相互作用触发了一个涉及PLC、PI3K/Akt和Ras/MAPK信号通路的信号级联反应。新出现的证据表明,神经营养支持减少、Trk受体表达变化或信号级联反应中断在包括阿尔茨海默病(AD)、帕金森病(PD)、亨廷顿舞蹈病(HD)、自闭症谱系障碍(ASD)等多种神经系统疾病的发展中起关键作用。本综述特别探讨了在各种脑部疾病背景下针对Trk受体、其配体和Trk信号的治疗方法。我们关注调节或抑制Trk受体作为脑部疾病治疗策略的潜力。