Cerebral dopamine neurotrophic factor protects H9c2 cardiomyocytes from apoptosis

Liu, H; Yu, Chenjie; Yu, Hao; Zhong, Lin; Wang, Y; Liu, J; Zhang, S; Sun, Jing; Lin, Dan; Gong, Lei; Jiao, Yang

doi:10.1007/s00059-017-4564-3

Cited by 12 publications

(7 citation statements)

References 34 publications

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“…In ER stress-related disease models in vivo, expression of endogenous CDNF was reported to increase after cerebral or myocardial ischemia [ 67 , 68 ]. In vitro, ER stress-inducing tunicamycin treatment increased CDNF expression in cardiomyocytes [ 69 ] but not in an osteosarcoma-derived cell line [ 58 ]. Thus, responsiveness of CDNF to ER stress may depend on cell type.…”

Section: Introductionmentioning

confidence: 99%

Cerebral dopamine neurotrophic factor protects and repairs dopamine neurons by novel mechanism

Lindholm

Saarma

2021

Mol Psychiatry

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Midbrain dopamine neurons deteriorate in Parkinson’s disease (PD) that is a progressive neurodegenerative movement disorder. No cure is available that would stop the dopaminergic decline or restore function of injured neurons in PD. Neurotrophic factors (NTFs), e.g., glial cell line-derived neurotrophic factor (GDNF) are small, secreted proteins that promote neuron survival during mammalian development and regulate adult neuronal plasticity, and they are studied as potential therapeutic agents for the treatment of neurodegenerative diseases. However, results from clinical trials of GDNF and related NTF neurturin (NRTN) in PD have been modest so far. In this review, we focus on cerebral dopamine neurotrophic factor (CDNF), an unconventional neurotrophic protein. CDNF delivered to the brain parenchyma protects and restores dopamine neurons in animal models of PD. In a recent Phase I-II clinical trial CDNF was found safe and well tolerated. CDNF deletion in mice led to age-dependent functional changes in the brain dopaminergic system and loss of enteric neurons resulting in slower gastrointestinal motility. These defects in Cdnf−/− mice intriguingly resemble deficiencies observed in early stage PD. Different from classical NTFs, CDNF can function both as an extracellular trophic factor and as an intracellular, endoplasmic reticulum (ER) luminal protein that protects neurons and other cell types against ER stress. Similarly to the homologous mesencephalic astrocyte-derived neurotrophic factor (MANF), CDNF is able to regulate ER stress-induced unfolded protein response (UPR) signaling and promote protein homeostasis in the ER. Since ER stress is thought to be one of the pathophysiological mechanisms contributing to the dopaminergic degeneration in PD, CDNF, and its small-molecule derivatives that are under development may provide useful tools for experimental medicine and future therapies for the treatment of PD and other neurodegenerative protein-misfolding diseases.

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Section: Introductionmentioning

confidence: 99%

Cerebral dopamine neurotrophic factor protects and repairs dopamine neurons by novel mechanism

Lindholm

Saarma

2021

Mol Psychiatry

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“…But for CDNF, there has not found any ER stress response element in the CDNF promoter and little significant found has been reported about the effect of CDNF in ER stress. Our recently study has found that CDNF expression can be upregulated by tunicamycin in H9c2 cells and CDNF overexpression can protect H9c2 cells from apoptosis induced by tunicamycin (in press) (Liu et al, ). But whether this protective role of CDNF on H9c2 is related with ER stress still need more studies.…”

Section: Discussionmentioning

confidence: 99%

Quantitative analysis on secretion level of CDNF regulated by two key α‐helices in CDNF protein

Líu

Zhong

Zhao

et al. 2019

Cell Biology International

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Cerebral dopamine neurotrophic factor (CDNF) has been considered as potent candidates for the therapy of Parkinson's disease (PD) for which can promote the survival of midbrain dopaminergic neurons. In addition to secret out from cells like other classical neurotrophic factors (NTFs), CDNF can locate in the endoplasmatic reticulum (ER), where they can function as ER stress response protein to regulate ER stress. In our previous studies, we have found two helices, a1 and a7, which can regulate the intracellular trafficking and secretion of CDNF. a1 distruction can significantly retain CDNF protein in the ER, but a7 distruction induce most CDNF protein secreting out the cells. Then a1 and a7 regulate protein trafficking and secretion in opposite side. However, the exact secretion level of CDNF affected by a1 or a7 have not been sensitively quantified. In this study, we used nanoluciferase to quantify the secretion level of CDNF protein so that we could evaluate the impact of a1 and a7 on CDNF secretion or function.

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“…Although MANF and CDNF were initially discovered by their neurotrophic activities, further studies revealed that MANF and CDNF are highly expressed in non-neural tissues and that their cytoprotective activity extends beyond the dopaminergic system ( Tadimalla et al, 2008 , Airavaara et al, 2009 ; Glembotski et al, 2012 ; Lindahl et al, 2014 ; Yang et al, 2014 ; Neves et al, 2016 ; Gao et al, 2017 ; Liu et al, 2018 ; Lu et al, 2018 ; Matlik et al, 2018 ). Moreover, MANF is found in circulation in the blood and it has been associated with several non-neuronal diseases in humans, including inflammatory diseases ( Wang et al, 2014 ; Chen et al, 2015 ; Yavarna et al, 2015 ; Galli et al, 2016 ), suggesting a role beyond neuroprotection.…”

Section: Manf and Cdnf In Immune Cell Signalingmentioning

confidence: 99%

“…MANF and CDNF were initially discovered by their neuroprotective activities in dopaminergic neurons in vitro and in vivo ( Petrova et al, 2003 ; Lindholm et al, 2007 ; Voutilainen et al, 2009 ) and thus classified as NTFs. However, these molecules are structurally distinct from all other classes of NTFs, signal through a yet unknown receptor/mechanism ( Lindahl et al, 2017 ) and their physiological activity extends beyond the nervous system ( Tadimalla et al, 2008 ; Glembotski et al, 2012 ; Lindahl et al, 2014 ; Chen et al, 2015 ; Liu et al, 2018 ). Moreover, similarly, to what has been found for neuropoietic cytokines, MANF and CDNF also play important roles in the regulation of immune responses ( Zhao et al, 2014 ; Chen et al, 2015 ; Neves et al, 2016 ) and this immune modulatory function is essential for their biological activity in vivo , promoting neuroprotection and regenerative success ( Neves et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Trophic Factors in Inflammation and Regeneration: The Role of MANF and CDNF

2018

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Regeneration is an important process in multicellular organisms, responsible for homeostatic renewal and repair of different organs after injury. Immune cell activation is observed at early stages of the regenerative response and its regulation is essential for regenerative success. Thus, immune regulators play central roles in optimizing regenerative responses. Neurotrophic factors (NTFs) are secreted molecules, defined by their ability to support neuronal cell types. However, emerging evidence suggests that they can also play important functions in the regulation of immune cell activation and tissue repair. Here we discuss the literature supporting a role of NTFs in the regulation of inflammation and regeneration. We will focus, in particular, in the emerging roles of mesencephalic astrocyte-derived neurotrophic factor (MANF) and cerebral dopamine neurotrophic factor (CDNF) in the regulation of immune cell function and in the central role that immune modulation plays in their biological activity in vivo. Finally, we will discuss the potential use of these factors to optimize regenerative success in vivo, both within and beyond the nervous system.

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Cerebral dopamine neurotrophic factor protects H9c2 cardiomyocytes from apoptosis

Abstract: The findings presented here contribute toward identifying the physiological functions of CDNF in cardiovascular diseases.

Cited by 12 publications

References 34 publications

Cerebral dopamine neurotrophic factor protects and repairs dopamine neurons by novel mechanism

Cerebral dopamine neurotrophic factor protects and repairs dopamine neurons by novel mechanism

Quantitative analysis on secretion level of CDNF regulated by two key α‐helices in CDNF protein

Trophic Factors in Inflammation and Regeneration: The Role of MANF and CDNF

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