Abstract

The cerebral dopamine neurotrophic factor (CDNF) together with the mesencephalic astrocyte-derived neurotrophic factor (MANF) form a unique family of neurotrophic factors (NTFs) structurally and functionally different from other proteins with neurotrophic activity. CDNF has no receptors on the cell membrane, is localized mainly in the cavity of endoplasmic reticulum (ER), and its primary function is to regulate ER stress. In addition, CDNF is able to suppress inflammation and apoptosis. Due to its functions, CDNF has demonstrated outstanding protective and restorative properties in various models of neuropathology associated with ER stress, including Parkinson’s disease (PD). That is why CDNF already passed clinical trials in patients with PD. However, despite the name, CDNF functions extend far beyond the dopamine system in the brain. In particular, there are data on participation of CDNF in the maturation and maintenance of other neurotransmitter systems, regulation of the processes of neuroplasticity and non-motor behavior. In the present review, we discuss the features of CDNF structure and functions, its protective and regenerative properties.

中文翻译：

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脑多巴胺神经营养因子 (CDNF)：结构、功能和治疗潜力

摘要

大脑多巴胺神经营养因子 (CDNF) 与中脑星形胶质细胞衍生的神经营养因子 (MANF) 一起形成了一个独特的神经营养因子 (NTF) 家族，在结构和功能上与其他具有神经营养活性的蛋白质不同。CDNF在细胞膜上没有受体，主要定位于内质网（ER）腔，其主要功能是调节内质网应激。此外，CDNF 能够抑制炎症和细胞凋亡。由于其功能，CDNF 在与 ER 应激相关的各种神经病理学模型中表现出出色的保护和恢复特性，包括帕金森病 (PD)。这就是为什么 CDNF 已经通过了 PD 患者的临床试验。然而，尽管名称如此，CDNF 的功能远远超出了大脑中的多巴胺系统。特别是，有关于 CDNF 参与其他神经递质系统的成熟和维持、调节神经可塑性和非运动行为过程的数据。在本综述中，我们讨论了 CDNF 结构和功能的特征、其保护和再生特性。