Trophic activities of endoplasmic reticulum proteins CDNF and MANF.
Trophic activities of endoplasmic reticulum proteins CDNF and MANF.
复制标题
DOI：
10.1007/s00441-020-03263-0
复制
发表时间：
2020-10
影响因子：
3.6
通讯作者：
中科院分区：
文献类型：
--
作者：
中脑星形胶质细胞源性神经营养因子（MANF）和脑多巴胺神经营养因子（CDNF）是内质网（ER）腔蛋白，在多种病理条件下在广泛的组织中赋予营养活性。尽管最初被归类为神经营养因子，但蛋白质在结构上和功能上都不类似于真正的神经营养因子。它们的高度同源结构由N-末端内的独特球状鞘脂激活蛋白样结构域组成，该结构域通过柔性接头连接至含有SAP样结构域、CXXC基序和ER保留序列的C-末端。神经营养因子通过与质膜中的同源受体结合来发挥作用，然而尚未鉴定出MANF和CDNF的细胞表面受体。两者都可以作为未折叠蛋白反应（UPR）基因，调节UPR和炎症过程。MANF和CDNF的营养活性延伸到中枢神经系统之外，其中MANF对于胰腺β细胞的发育至关重要，并且两者都在与肝脏、心脏、骨骼组织、肾脏和外周神经系统相关的多种疾病中具有营养作用。本文就MANF和CDNF的结构特点、与内质网应激和炎症反应的作用机制等方面进行综述。最近确定的相互作用与脂质和膜贩运也将被描述。最后，他们的功能和治疗潜力，在不同的疾病，包括最近的临床试验使用CDNF治疗帕金森氏病将进行讨论。总的来说，这篇综述将突出MANF和CDNF作为调节内质网功能的广泛作用的营养因子。
Mesencephalic astrocyte-derived neurotrophic factor (MANF) and cerebral dopamine neurotrophic factor (CDNF) are endoplasmic reticulum (ER) luminal proteins that confer trophic activities in a wide range of tissues under diverse pathological conditions. Despite initially being classified as neurotrophic factors, neither protein structurally nor functionally resembles bona fide neurotrophic factors. Their highly homologous structures are comprised of a unique globular, saposin-like domain within the N-terminus joined by a flexible linker to a C-terminus containing a SAP-like domain, CXXC motif and an ER retention sequence. Neurotrophic factors exert effects by binding to cognate receptors in the plasma membrane, however no cell surface receptors have been identified for MANF and CDNF. Both can act as unfolded protein response (UPR) genes that modulate the UPR and inflammatory processes. The trophic activity of MANF and CDNF extends beyond the central nervous system with MANF being crucial for the development of pancreatic β-cells and both have trophic effects in a variety of diseases related to the liver, heart, skeletal tissue, kidney, and peripheral nervous system. In this article, the unique features of MANF and CDNF, such as their structure and mechanisms of action related to ER stress and inflammation will be reviewed. Recently identified interactions with lipids and membrane trafficking will also be described. Lastly, their function and therapeutic potential in different diseases including a recent clinical trial using CDNF to treat Parkinson’s disease will be discussed. Collectively, this review will highlight MANF and CDNF as broad-acting trophic factors that regulate functions of the endoplasmic reticulum.
登录
查看更多内容
影响因子：
3.7
作者：
Cameron TL;Bell KM;Tatarczuch L;Mackie EJ;Rajpar MH;McDermott BT;Boot-Handford RP;Bateman JF
通讯作者：
Bateman JF
影响因子：
4.3
作者：
Galli, Emilia;Planken, Anu;Lindholm, Paivi
通讯作者：
Lindholm, Paivi
DOI：
10.1002/cne.22039
发表时间：
2009-07-01
期刊：
The Journal of comparative neurology
影响因子：
--
作者：
Airavaara M;Shen H;Kuo CC;Peränen J;Saarma M;Hoffer B;Wang Y
通讯作者：
Wang Y
DOI：
10.1016/j.bbamcr.2018.08.012
发表时间：
2018-11-01
影响因子：
5.1
作者：
Arancibia, Duxan;Zamorano, Pedro;Estela Andres, Maria
通讯作者：
Estela Andres, Maria
DOI：
10.1073/pnas.68.10.2417
发表时间：
1971-01-01
影响因子：
11.1
作者：
ANGELETT.RH;BRADSHAW, RA
通讯作者：
BRADSHAW, RA