Department of Neuroscience Rita Levi Montalcini, University of Turin, 10126 Turin, Italy.
Laboratory of Brain Development and Disease, Neuroscience Institute Cavalieri Ottolenghi, University of Turin, 10043 Orbassano, Italy.
Int J Mol Sci. 2020 Dec 24;22(1):136. doi: 10.3390/ijms22010136.
The neuromuscular junction (NMJ) is at the crossroad between the nervous system (NS) and the muscle. Following neurotransmitter release from the motor neurons (MNs), muscle contraction occurs and movement is generated. Besides eliciting muscle contraction, the NMJ represents a site of chemical bidirectional interplay between nerve and muscle with the active participation of Schwann cells. Indeed, signals originating from the muscle play an important role in synapse formation, stabilization, maintenance and function, both in development and adulthood. We focus here on the contribution of the Glial cell line-Derived Neurotrophic Factor (GDNF) to these processes and to its potential role in the protection of the NMJ during neurodegeneration. Historically related to the maintenance and survival of dopaminergic neurons of the , GDNF also plays a fundamental role in the peripheral NS (PNS). At this level, it promotes muscle trophism and it participates to the functionality of synapses. Moreover, compared to the other neurotrophic factors, GDNF shows unique peculiarities, which make its contribution essential in neurodegenerative disorders. While describing the known structural and functional changes occurring at the NMJ during neurodegeneration, we highlight the role of GDNF in the NMJ-muscle cross-talk and we review its therapeutic potential in counteracting the degenerative process occurring in the PNS in progressive and severe diseases such as Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA). We also describe functional 3D neuromuscular co-culture systems that have been recently developed as a model for studying both NMJ formation in vitro and its involvement in neuromuscular disorders.
神经肌肉接头（NMJ）位于神经系统（NS）和肌肉之间的交叉路口。运动神经元（MNs）释放神经递质后，肌肉收缩，运动产生。NMJ 不仅引发肌肉收缩，还是神经和肌肉之间化学双向相互作用的场所，其中雪旺细胞（Schwann cells）积极参与。事实上，源自肌肉的信号在突触形成、稳定、维持和功能方面发挥着重要作用，无论是在发育过程中还是在成年期。我们这里重点关注胶质细胞源性神经营养因子（GDNF）对这些过程的贡献及其在神经退行性变过程中保护 NMJ 的潜在作用。GDNF 历史上与多巴胺能神经元的维持和存活有关，在周围神经系统（PNS）中也起着至关重要的作用。在这一水平上，它促进肌肉营养，并参与突触的功能。此外，与其他神经营养因子相比，GDNF 具有独特的特点，使其在神经退行性疾病中的贡献至关重要。在描述神经退行性变过程中 NMJ 发生的已知结构和功能变化时，我们强调了 GDNF 在 NMJ-肌肉交叉对话中的作用，并回顾了其在对抗进行性和严重疾病（如阿尔茨海默病（AD）、肌萎缩侧索硬化症（ALS）和脊髓性肌萎缩症（SMA））中 PNS 退行性过程中的治疗潜力。我们还描述了最近开发的功能性 3D 神经肌肉共培养系统，该系统可作为体外研究 NMJ 形成及其在神经肌肉疾病中的作用的模型。
