Didn't read through it all, but MANF seems to help cleavage
http://www.jns-journal.com/article/PIIS002251...2/abstract
Mesencephalic astrocyte-derived neurotrophic factor prevents neuron loss via inhibiting ischemia-induced apoptosis
Wen Yang
AffiliationsSchool of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaBiopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaThese authors contributed equally to this work.
, Yujun Shen
AffiliationsSchool of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaBiopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaThese authors contributed equally to this work.
, Ying Chen
AffiliationsSchool of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaBiopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaThese authors contributed equally to this work.
, Lu Chen
AffiliationsSchool of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaBiopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. China
, Le Wang
AffiliationsDepartment of Radiology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui, P.R. China
, Haiping Wang
AffiliationsSchool of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaBiopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. China
, Shengchun Xu
AffiliationsSchool of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. China
, Shengyun Fang
AffiliationsSchool of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaBiopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. China
, Yu Fu
AffiliationsBiopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. China
, Yongqiang Yu
AffiliationsDepartment of Radiology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui, P.R. ChinaCorrespondence to: Y. Yu, 218 Jixi Road, The First Affiliated Hospital of Anhui Medical University, Hefei 230022. Tel./fax: +86 551 62922381.
, Yuxian Shen
AffiliationsSchool of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaBiopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaCorrespondence to: Y. Shen, 81 Meishan Road, Anhui Medical University, Hefei 230032. Tel.: +86 551 65161121; fax: +86 551 65161126.
Received 27 November 2013; received in revised form 15 June 2014; accepted 19 June 2014. published online 30 June 2014.
Accepted Manuscript
Abstract Full Text PDFImages References .Abstract
Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) has been shown to be up -regulated under the focal cerebral ischemia and protected against ischemic injury in rats. However, the underlying mechanisms are unclear. The aim of this study was to verify the protection of MANF on the cerebral ischemic injury and further investigate the possible mechanisms. Rat focal ischemic model was established by middle cerebral artery occlusion (MCAO). The recombinant human MANF was therapeutically administrated to the ipsilateral ventricle at 2hrs after MCAO. MANF decreased the number of the propidium iodide (PI)- and TUNEL-positive neural cells. Contrarily, MANF protected the NeuN-positive cells in hippocampus and cortex from death induced by ischemia. The more interesting results in this study were that MANF repressed the cleavage of caspase-3 triggered by focal cerebral ischemia. MANF also reduced the elevated levels of BIP/Grp78, phosphorylated IRE1, and splicing XBP1 induced by focal cerebral ischemia, but not affect CHOP expression. Meanwhile, focal cerebral ischemia elevated the levels of XBP1 mRNA, including unspliced XBP1 (XBP1u) and spliced XBP1 (XBP1s). However, MANF did not affect the expression of XBP1 mRNA, neither XBP1u nor XBP1s. These results suggest that MANF can prevent the neuron loss via inhibiting ischemia-induced apoptosis and regulating unfolded protein response-related genes.
http://www.jns-journal.com/article/PIIS002251...2/abstract
Mesencephalic astrocyte-derived neurotrophic factor prevents neuron loss via inhibiting ischemia-induced apoptosis
Wen Yang
AffiliationsSchool of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaBiopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaThese authors contributed equally to this work.
, Yujun Shen
AffiliationsSchool of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaBiopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaThese authors contributed equally to this work.
, Ying Chen
AffiliationsSchool of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaBiopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaThese authors contributed equally to this work.
, Lu Chen
AffiliationsSchool of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaBiopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. China
, Le Wang
AffiliationsDepartment of Radiology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui, P.R. China
, Haiping Wang
AffiliationsSchool of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaBiopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. China
, Shengchun Xu
AffiliationsSchool of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. China
, Shengyun Fang
AffiliationsSchool of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaBiopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. China
, Yu Fu
AffiliationsBiopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. China
, Yongqiang Yu
AffiliationsDepartment of Radiology, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui, P.R. ChinaCorrespondence to: Y. Yu, 218 Jixi Road, The First Affiliated Hospital of Anhui Medical University, Hefei 230022. Tel./fax: +86 551 62922381.
, Yuxian Shen
AffiliationsSchool of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaBiopharmaceutical Research Institute, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, P.R. ChinaCorrespondence to: Y. Shen, 81 Meishan Road, Anhui Medical University, Hefei 230032. Tel.: +86 551 65161121; fax: +86 551 65161126.
Received 27 November 2013; received in revised form 15 June 2014; accepted 19 June 2014. published online 30 June 2014.
Accepted Manuscript
Abstract Full Text PDFImages References .Abstract
Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) has been shown to be up -regulated under the focal cerebral ischemia and protected against ischemic injury in rats. However, the underlying mechanisms are unclear. The aim of this study was to verify the protection of MANF on the cerebral ischemic injury and further investigate the possible mechanisms. Rat focal ischemic model was established by middle cerebral artery occlusion (MCAO). The recombinant human MANF was therapeutically administrated to the ipsilateral ventricle at 2hrs after MCAO. MANF decreased the number of the propidium iodide (PI)- and TUNEL-positive neural cells. Contrarily, MANF protected the NeuN-positive cells in hippocampus and cortex from death induced by ischemia. The more interesting results in this study were that MANF repressed the cleavage of caspase-3 triggered by focal cerebral ischemia. MANF also reduced the elevated levels of BIP/Grp78, phosphorylated IRE1, and splicing XBP1 induced by focal cerebral ischemia, but not affect CHOP expression. Meanwhile, focal cerebral ischemia elevated the levels of XBP1 mRNA, including unspliced XBP1 (XBP1u) and spliced XBP1 (XBP1s). However, MANF did not affect the expression of XBP1 mRNA, neither XBP1u nor XBP1s. These results suggest that MANF can prevent the neuron loss via inhibiting ischemia-induced apoptosis and regulating unfolded protein response-related genes.
