Cerebral dopamine neurotrophic factor (CDNF) is an endogenous protein in humans and other vertebrates, and it has been shown to have protective and restorative effects on cells in various disease models. Although it is named as a neurotrophic factor, its actions are drastically different from classical neurotrophic factors such as neurotrophins or the glial cell line-derived neurotrophic family of proteins. Like all secreted proteins, CDNF has a signal sequence at the N-terminus, but unlike common growth factors it has a KDEL-receptor retrieval sequence at the C-terminus. Thus, CDNF is mainly located in the ER. In response to adverse effects, such as ER stress, the expression of CDNF is upregulated and can alleviate ER stress. Also different from other neurotrophic factors, CDNF reduces protein aggregation and inflammation in disease models. Although it is an ER luminal protein, it can surprisingly directly interact with alpha-synuclein, a protein involved in the pathogenesis of synucleinopathies e.g., Parkinson's disease. Pleiotropic CDNF has therapeutic potential and has been tested as a recombinant human protein and gene therapy. The neuroprotective and neurorestorative effects have been described in a number of preclinical studies of Parkinson's disease, stroke and amyotrophic lateral sclerosis. Currently, it was successfully evaluated for safety in a phase 1/2 clinical trial for Parkinson's disease. Collectively, based on recent findings on the mode of action and therapeutic potential of CDNF, its use as a drug could be expanded to other ER stress-related diseases.

脑多巴胺神经营养因子（CDNF）是人类和其他脊椎动物的内源性蛋白质，已被证明对各种疾病模型中的细胞具有保护和恢复作用。尽管它被命名为神经营养因子，但其作用与经典神经营养因子（例如神经营养蛋白或神经胶质细胞系衍生的神经营养蛋白家族）截然不同。与所有分泌蛋白一样，CDNF 在 N 末端有一个信号序列，但与常见的生长因子不同，它在 C 末端有一个 KDEL 受体恢复序列。因此，CDNF主要位于ER中。为了应对不利影响，例如 ER 应激，CDNF 的表达上调，可以缓解 ER 应激。与其他神经营养因子不同的是，CDNF 可以减少疾病模型中的蛋白质聚集和炎症。尽管它是一种内质网腔蛋白，但令人惊讶的是，它可以直接与α-突触核蛋白相互作用，α-突触核蛋白是参与突触核蛋白病（例如帕金森病）发病机制的蛋白质。多效性 CDNF 具有治疗潜力，并已作为重组人类蛋白质和基因疗法进行了测试。帕金森病、中风和肌萎缩侧索硬化症的许多临床前研究已经描述了神经保护和神经恢复作用。目前，其在帕金森病的1/2期临床试验中成功评估了安全性。总的来说，根据最近对 CDNF 的作用方式和治疗潜力的发现，其作为药物的用途可以扩展到其他与 ER 应激相关的疾病。