STRAP和NME1介导神经营养因子GDF5的神经突生长促进作用。

STRAP and NME1 Mediate the Neurite Growth-Promoting Effects of the Neurotrophic Factor GDF5.

作者信息

Anantha Jayanth, Goulding Susan R, Wyatt Sean L, Concannon Ruth M, Collins Louise M, Sullivan Aideen M, O'Keeffe Gerard W

机构信息

Department of Anatomy & Neuroscience, University College Cork (UCC), Cork, Ireland.

Department of Biological Sciences, Cork Institute of Technology, Cork, Ireland.

出版信息

iScience. 2020 Aug 12;23(9):101457. doi: 10.1016/j.isci.2020.101457. eCollection 2020 Sep 25.

Loss of midbrain dopaminergic (mDA) neurons and their axons is central to Parkinson's disease (PD). Growth differentiation factor (GDF)5 is a potential neurotrophic factor for PD therapy. However, the molecular mediators of its neurotrophic action are unknown. Our proteomics analysis shows that GDF5 increases the expression of serine threonine receptor-associated protein kinase (STRAP) and nucleoside diphosphate kinase (NME)1 in the SH-SY5Y neuronal cell line. GDF5 overexpression increased NME1 expression in adult rat brain . NME and STRAP mRNAs are expressed in developing and adult rodent midbrain. Expression of both STRAP and NME1 is necessary and sufficient for the promotion of neurite growth in SH-SY5Y cells by GDF5. NME1 treatment increased neurite growth in both SH-SY5Y cells and cultured mDA neurons. Expression patterns of NME and STRAP are altered in PD midbrain. NME1 and STRAP are thus key mediators of GDF5's neurotrophic effects, rationalizing their future study as therapeutic targets for PD.

中脑多巴胺能（mDA）神经元及其轴突的丧失是帕金森病（PD）的核心问题。生长分化因子（GDF）5是一种用于PD治疗的潜在神经营养因子。然而，其神经营养作用的分子介质尚不清楚。我们的蛋白质组学分析表明，GDF5可增加SH-SY5Y神经细胞系中丝氨酸苏氨酸受体相关蛋白激酶（STRAP）和核苷二磷酸激酶（NME）1的表达。GDF5过表达可增加成年大鼠脑中NME1的表达。NME和STRAP mRNA在发育中和成年啮齿动物中脑表达。STRAP和NME1的表达对于GDF5促进SH-SY5Y细胞中的神经突生长是必要且充分的。NME1处理可增加SH-SY5Y细胞和培养的mDA神经元中的神经突生长。PD中脑NME和STRAP的表达模式发生改变。因此，NME1和STRAP是GDF5神经营养作用的关键介质，这使它们作为PD治疗靶点的未来研究具有合理性。