Mesencephalic astrocyte-derived neurotrophic factor prevents neuron loss via inhibiting ischemia-induced apoptosis

Yang, Wen; Shen, Yujun; Chen, Ying; Lu, Ciyong; Wang, Le; Wang, Haiping; Xu, Shunqing; Fang, Shengyun; Fu, Yu; Yan, Yu

doi:10.1016/j.jns.2014.06.042

Cited by 65 publications

(66 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It can be differently regulated by epileptic and ischemic insults in the rodent brain and heart (Apostolou et al, 2008; Lindholm et al, 2008; Tadimalla et al, 2008). Besides, large studies indicate that MANF can not only protect cultured nigral dopaminergic neurons and suppress cell proliferation and ERS-induced cell death, but also can affect cell morphology and size in non-neuronal cells (Petrova et al, 2004; Lindholm et al, 2007; Airavaara et al, 2009; Palgi et al, 2009; Voutilainen et al, 2009; Yu et al, 2010; Commissiong, 2012; Shen et al, 2012; Zhao et al, 2013; Yang et al, 2014; Cordero-Llana et al, 2015; Liu et al, 2015). Moreover, recently reported on science displayed that intravitreal injection recombinant MANF could promote alternative activation of innate immune cells, enhance neuroprotection and tissue repair, and improve the success of photoreceptor replacement therapies in the retina (Neves et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Expression and Distribution of Mesencephalic Astrocyte-Derived Neurotrophic Factor in the Retina and Optic Nerve

Gao

Zhang

et al. 2017

Front. Hum. Neurosci.

View full text Add to dashboard Cite

Mesencephalic astrocyte-derived neurotrophic factor (MANF), otherwise named Arginine-Rich, Mutated in Early-stage Tumors (ARMET), is a secretory endoplasmic reticulum stress (ERS) protein that is widely expressed in mammalian tissues. To date, little is known about the distribution and expression of MANF in the retina and optic nerve (ON). Therefore, we studied the expression and distribution of MANF in the ON and retina by real-time PCR, immunofluorescence staining and western blotting. Results from rat and mouse were highly consistent in the retina. MANF was detected in both tissues in rat, wherein it was principally localized to the ganglion cell layer (GCL), followed by the inner nuclear layer (INL). The MANF protein levels in the rat retina were 3.33-fold higher than in the rat ON. Additionally, MANF was robustly expressed by retinal ganglion cells (RGCs) in the human retina. In human ON, MANF was partially co-localized with glial fibrillary acidic protein (GFAP), suggesting that it was not restricted to astrocytes. In vitro studies confirmed that MANF could be robustly expressed in RGCs and was found principally within the cytoplasm. Hypoxia can stimulate up-regulation by of MANF expression over time, suggesting that MANF may play a vital role in the functional regulation of RGCs both in health and disease. We believe that the present study improves our understanding of the distribution and expression of MANF in the retina and ON and could help in further analysis of its interact and correlate with the relevant ophthalmic diseases.

show abstract

Section: Discussionmentioning

confidence: 99%

Expression and Distribution of Mesencephalic Astrocyte-Derived Neurotrophic Factor in the Retina and Optic Nerve

Gao

Zhang

et al. 2017

Front. Hum. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The neuroprotective effect of MANF is mediated, at least in part, through attenuation of ischemia-mediated cell apoptosis 56 . In addition, ipsilateral ventricle injection of human recombinant MANF 2 hours after MCAO rescues the cerebral ischemia-induced neuron loss and promotes behavioral recovery in rats, which is associated with inhibition of ischemia-induced upregulation of ERSR proteins including BiP, phosphorylated IRE1 and XBP1s, as well as suppression of caspase 3 cleavage 57 .…”

Section: Manf Functions (Table 1) and Underlying Mechanismsmentioning

confidence: 99%

Mesencephalic astrocyte-derived neurotrophic factor (MANF), a new player in endoplasmic reticulum diseases: structure, biology, and therapeutic roles

Kim

Park

Chen

2017

Translational Research

View full text Add to dashboard Cite

Mesencephalic astrocyte-derived neurotrophic factor (MANF), a newly identified 18 kDa soluble protein, localizes to the luminal endoplasmic reticulum (ER). ER stress can stimulate MANF expression and secretion. In Drosophila and zebrafish, MANF regulates dopaminergic neuron development. In contrast, in mice, MANF deficiency leads to diabetes and activation of the unfolded protein response. Recent studies in rodent models have demonstrated that MANF mitigates diabetes, exerts neurotrophic function in neurodegenerative disease, protects cardiomyocytes and neurons in myocardial infarction and cerebral ischemia, respectively, and promotes immune cell phenotype switch from proinflammatory macrophages to prorepair anti-inflammatory macrophages. The cytoprotective mechanisms of MANF upon ER stress are currently under active investigation. In addition, for the first time we have discovered that MANF can potentially serve as a urinary ER stress biomarker in ER stress-mediated kidney disease. These studies have underscored the diagnostic and therapeutic importance of MANF in ER diseases.

show abstract

“…Extracellularly, MANF, acting as a neurotrophic factor, plays a key role in regulating the development of the dopaminergic system in zebrafish and selectively supports and protects midbrain dopamine neurons in both mouse and rat models of Parkinson's disease [5,7,8]. As well, MANF can rescue cardiomyocytes and cortical neurons from ischemia-induced injury in vivo [9][10][11]. MANF expression was found increased in β-cell of diabetic Akita mice with ER stress induced by the accumulation of proinsulin in the ER [12].…”

Section: Blood Sampling and Variable Assessmentmentioning

confidence: 99%

Circulating mesencephalic astrocyte-derived neurotrophic factor is increased in newly diagnosed prediabetic and diabetic patients, and is associated with insulin resistance

Fang

Yang

et al. 2017

Endocr J

View full text Add to dashboard Cite

Mesencephalic astrocyte-derived neurotrophic factor prevents neuron loss via inhibiting ischemia-induced apoptosis

Cited by 65 publications

References 45 publications

Expression and Distribution of Mesencephalic Astrocyte-Derived Neurotrophic Factor in the Retina and Optic Nerve

Expression and Distribution of Mesencephalic Astrocyte-Derived Neurotrophic Factor in the Retina and Optic Nerve

Mesencephalic astrocyte-derived neurotrophic factor (MANF), a new player in endoplasmic reticulum diseases: structure, biology, and therapeutic roles

Circulating mesencephalic astrocyte-derived neurotrophic factor is increased in newly diagnosed prediabetic and diabetic patients, and is associated with insulin resistance

Contact Info

Product

Resources

About