TrkB Truncated Isoform Receptors as Transducers and Determinants of BDNF Functions.
TrkB Truncated Isoform Receptors as Transducers and Determinants of BDNF Functions.
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DOI：
10.3389/fnins.2022.847572
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发表时间：
2022
影响因子：
4.3
通讯作者：
Yanpallewar S
中科院分区：
文献类型：
--
作者：
Tessarollo L;Yanpallewar S
脑源性神经营养因子（BDNF）属于分泌性生长因子的神经营养蛋白家族，并且以高亲和力结合TrkB酪氨酸激酶受体。BDNF是脊椎动物中枢（CNS）和外周（PNS）神经系统发育的关键参与者，其对神经元的强促存活功能作为用于管理神经退行性疾病如肌萎缩性侧索硬化症（ALS）、亨廷顿病、帕金森病和阿尔茨海默病的潜在治疗靶点引起了极大的兴趣。TrkB基因，除了全长受体，编码许多亚型，包括一些缺乏催化酪氨酸激酶结构域。重要的是，这些截短的同种型之一，即TrkB.T1，是成人中表达最广泛的TrkB受体，这表明在BDNF信号传导的调节中起重要作用。虽然已经取得了一些进展，但TrkB.T1功能的机制在很大程度上仍然未知。在这里，我们批判性地审查目前的知识TrkB.T1的分布和功能，可能有助于我们了解它如何调节和参与BDNF信号在正常的生理和病理条件。
Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of secreted growth factors and binds with high affinity to the TrkB tyrosine kinase receptors. BDNF is a critical player in the development of the central (CNS) and peripheral (PNS) nervous system of vertebrates and its strong pro-survival function on neurons has attracted great interest as a potential therapeutic target for the management of neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS), Huntington, Parkinson’s and Alzheimer’s disease. The TrkB gene, in addition to the full-length receptor, encodes a number of isoforms, including some lacking the catalytic tyrosine kinase domain. Importantly, one of these truncated isoforms, namely TrkB.T1, is the most widely expressed TrkB receptor in the adult suggesting an important role in the regulation of BDNF signaling. Although some progress has been made, the mechanism of TrkB.T1 function is still largely unknown. Here we critically review the current knowledge on TrkB.T1 distribution and functions that may be helpful to our understanding of how it regulates and participates in BDNF signaling in normal physiological and pathological conditions.
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