Mesencephalic astrocyte‐derived neurotrophic factor reduces ischemic brain injury and promotes behavioral recovery in rats

Airavaara, Mikko; Shen, Hui; Kuo, Chi-Chung; Peränen, Johan; Saarma, Märt; Hoffer, Barry J.; Wang, Yun

doi:10.1002/cne.22039

Cited by 130 publications

(150 citation statements)

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“…Administration of MANF into the cerebral cortex before MCAO was able to significantly reduce the infarction volume and reduce markers of apoptotic cell death in the ischemic cortex (Airavaara et al, 2009). In support to that MANF protein added to the culture medium of cardiac myocytes prevented cell death induced by simulated ischemia in vitro .…”

Section: Cdnf and Manf Activities In Vivomentioning

confidence: 54%

“…Cerebral dopamine neurotrophic factor (CDNF; official name by HUGO gene nomenclature committee; previous name conserved dopamine NTF) and mesencephalic astrocyte-derived neurotrophic factor (MANF) form a novel evolutionary conserved protein family showing neurotrophic activities (Petrova et al, 2003;Lindholm et al, 2007Lindholm et al, , 2008Airavaara et al, 2009;Palgi et al, 2009;Voutilainen et al, 2009).…”

Section: Cdnf and Manf Ligandsmentioning

confidence: 99%

“…Furthermore, recombinant MANF protein protected cardiac myocytes from ischemia-induced death in vitro . In line, MANF protein protects against ischemic brain injury induced by middle cerebral artery occlusion (MCAO) in rats in vivo (Airavaara et al, 2009). The ER stress response element-II (ERSE-II) is located in the Armet promoter and is shown to regulate Armet expression (Mizobuchi et al, 2007).…”

Section: Protection Against Er Stressmentioning

confidence: 99%

“…Effects of recombinant MANF protein have also been studied in an experimental model of stroke in rats (Airavaara et al, 2009). Administration of MANF into the cerebral cortex before MCAO was able to significantly reduce the infarction volume and reduce markers of apoptotic cell death in the ischemic cortex (Airavaara et al, 2009).…”

Section: Cdnf and Manf Activities In Vivomentioning

confidence: 99%

“…Although CDNF and MANF have potent effects on adult midbrain dopaminergic system (Lindholm et al, 2007, Voutilainen et al, 2009) and cortical neurons in the ischemia model (Airavaara et al, 2009), it is currently unknown which other CNS or PNS neuronal cell types or non-neuronal cells CDNF and MANF may affect in vivo. GDNF was originally introduced as a specific NTF for midbrain dopaminergic neurons (Lin et al, 1993), but it is now clear that the claim of specificity is not valid.…”

Section: Potential Therapeutic Proteinsmentioning

confidence: 99%

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Novel CDNF/MANF family of neurotrophic factors

Lindholm

Saarma

2010

Developmental Neurobiology

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Current therapeutic interventions for neurodegenerative diseases alleviate only disease symptoms, while treatments that could stop or reverse actual degenerative processes are not available. Parkinson's disease (PD) is a movement disorder with characteristic degeneration of dopaminergic neurons in the midbrain. Few neurotrophic factors (NTFs) that promote survival, maintenance, and differentiation of affected brain neurons are considered as potential therapeutic agents for the treatment of neurodegenerative diseases. Thus, it is important to search and study new NTFs that could also be used in therapy. In this review, we discuss novel evolutionary conserved family of NTFs consisting of two members in the vertebrates, cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF). Invertebrates, including Drosophila and Caenorhabditis have a single protein homologous to vertebrate CDNF/ MANF. Characteristic feature of these proteins is eight structurally conserved cysteine residues, which determine the protein fold. The crystal structure analysis revealed that CDNF and MANF consist of two domains; an amino-terminal saposin-like domain that may interact with lipids or membranes, and a presumably unfolded carboxy-terminal domain that may protect cells against endoplasmic reticulum stress. CDNF and MANF protect midbrain dopaminergic neurons and restore motor function in 6-hydroxydopamine rat model of PD in vivo. In line, Drosophila MANF is needed for the maintenance of dopaminergic neurites and dopamine levels in the fly, suggesting that the function of CDNF/MANF proteins is evolutionary conserved. Future studies will reveal the receptors and mode of action of these novel factors, which are potential therapeutic proteins for the treatment of PD. ' 2010 Wiley Periodicals, Inc. Develop Neurobiol 70: 360-371, 2010

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Section: Cdnf and Manf Activities In Vivomentioning

confidence: 54%

Section: Cdnf and Manf Ligandsmentioning

confidence: 99%

Section: Protection Against Er Stressmentioning

confidence: 99%

Section: Cdnf and Manf Activities In Vivomentioning

confidence: 99%

Section: Potential Therapeutic Proteinsmentioning

confidence: 99%

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Novel CDNF/MANF family of neurotrophic factors

Lindholm

Saarma

2010

Developmental Neurobiology

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174

136

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MANF attenuates neuronal apoptosis and promotes behavioral recovery via Akt/MDM‐2/p53 pathway after traumatic spinal cord injury in rats

Gao

Fan³

et al. 2018

BioFactors

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The aim of this study was to investigate the potential effect and mechanism of action of MANF in attenuating neuronal apoptosis following t-SCI. A clip compressive model was used to induce a crush injury of the spinal cord in a total of 230 rats. The Basso, Beattie, and Bresnahan (BBB) score, spinal cord water content, and blood spinal cord barrier (BSCB) permeability were evaluated. The expression levels of MANF and its downstream proteins were examined by western blotting. Immunofluorescence staining of MANF, NeuN, GFAP, Iba-1, cleaved caspase-3, and TUNEL staining were also performed. Cells were counted in six randomly selected fields in the gray matter regions of the sections from two spinal cord sites (2 mm rostral and caudal to the epicenter of the injury) per sample. A cell-based mechanical injury model was also conducted using SH-SY5Y cells. Cell apoptosis and viability were assessed by flow cytometry, an MTT assay, and trypan blue staining. Subcellular structures were observed by transmission electron microscopy. MANF was mainly expressed in neurons. The expression levels of MANF, and its downstream target, p-Akt, were gradually increased and after t-SCI. Treatment with MANF increased Bcl-2 and decreased Bax and CC-3 levels; these effects were reversed on treatment with MK2206. The BBB score, spinal cord water content, and BSCB destruction were also ameliorated by MANF treatment. MANF decreases neuronal apoptosis and improves neurological function through Akt/MDM-2/p53 pathway after t-SCI. Therefore, MANF might be a potential treatment for patients with t-SCI.© 2018 BioFactors, 2018.

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The developmental neurotoxicity of polybrominated diphenyl ethers: Effect of DE‐71 on dopamine in zebrafish larvae

Wang

Yang

et al. 2015

Enviro Toxic and Chemistry

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Abstract:The potential neurotoxicity of polybrominated diphenyl ethers (PBDEs) is still a great concern. In the present study, we investigated whether exposure to PBDEs could affect the neurotransmitter system and cause developmental neurotoxicity in zebrafish. Two hours post fertilization (hpf) zebrafish embryos were exposed to different concentrations of the PBDE mixture DE-71 (0-100 µg/L). The larvae were harvested at 120 hpf and the impact on dopaminergic signaling was investigated. The results revealed significant reductions of whole-body dopamine (DA) content and its metabolite, dihydroxyphenylacetic acid (DOPAC) content in DE-71-exposed larvae. The transcription of genes involved in the development of dopaminergic neurons (e.g. manf, bdnf, and nr4a2b) was significantly down-regulated upon exposure to DE-71. DE-71 also resulted in a significant decrease of tyrosine hydroxylase (TH) and dopamine transporter protein levels in dopaminergic neurons. The expression level of TH in forebrain neurons was assessed by whole-mount immunofluorescence, and the results further demonstrated that the TH protein expression level was reduced in dopaminergic neurons. In addition to these molecular changes, we also observed reduced locomotor activity in DE-71-exposed larvae. Taken together, the present study demonstrates that acute exposure to PBDEs can affect dopaminergic signaling through disrupting the synthesis and transportation of dopamine in zebrafish, thereby disrupting normal neurodevelopment.In accord with its experimental findings, this study extends our knowledge of the mechanisms governing PBDE-induced developmental neurotoxicity. This article is protected by copyright. All rights reserved

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Mesencephalic astrocyte‐derived neurotrophic factor reduces ischemic brain injury and promotes behavioral recovery in rats

Cited by 130 publications

References 34 publications

Novel CDNF/MANF family of neurotrophic factors

Novel CDNF/MANF family of neurotrophic factors

MANF attenuates neuronal apoptosis and promotes behavioral recovery via Akt/MDM‐2/p53 pathway after traumatic spinal cord injury in rats

The developmental neurotoxicity of polybrominated diphenyl ethers: Effect of DE‐71 on dopamine in zebrafish larvae

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