PEP-1-PEA-15 protects against toxin-induced neuronal damage in a mouse model of Parkinson's disease

Ahn, Eun Hee; Kim, Dae Won; Shin, Min Jea; Kim, Hye Ri; Kim, So Mi; Woo, Su Jung; Eom, Seon Ae; Jo, Hyo Sang; Kim, Duk‐Soo; Cho, Sung‐Woo; Park, Jinseu; Eum, Won Sik; Choi, Soo Young

doi:10.1016/j.bbagen.2014.01.004

Cited by 17 publications

(15 citation statements)

References 66 publications

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“…Microglial γ‐enolase is neuroprotective in a mouse model of AD (Hafner et al ., 2013). Astrocyte protein PEA‐15 protects neuronal cells in vitro against MPTP‐induced dopaminergic cell death (a model of PD) and raises dopamine levels in mouse striatum in vivo (Ahn et al ., 2014). Aspartate aminotransferase and aldolase are major targets for deglycation repair by DJ‐1, which is highly induced in many cases of PD (Richarme et al ., 2015).…”

Section: Discussionmentioning

confidence: 99%

Proteins that mediate protein aggregation and cytotoxicity distinguish Alzheimer's hippocampus from normal controls

et al. 2016

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SummaryNeurodegenerative diseases are distinguished by characteristic protein aggregates initiated by disease‐specific ‘seed’ proteins; however, roles of other co‐aggregated proteins remain largely unexplored. Compact hippocampal aggregates were purified from Alzheimer's and control‐subject pools using magnetic‐bead immunoaffinity pulldowns. Their components were fractionated by electrophoretic mobility and analyzed by high‐resolution proteomics. Although total detergent‐insoluble aggregates from Alzheimer's and controls had similar protein content, within the fractions isolated by tau or Aβ1–42 pulldown, the protein constituents of Alzheimer‐derived aggregates were more abundant, diverse, and post‐translationally modified than those from controls. Tau‐ and Aβ‐containing aggregates were distinguished by multiple components, and yet shared >90% of their protein constituents, implying similar accretion mechanisms. Alzheimer‐specific protein enrichment in tau‐containing aggregates was corroborated for individuals by three analyses. Five proteins inferred to co‐aggregate with tau were confirmed by precise in situ methods, including proximity ligation amplification that requires co‐localization within 40 nm. Nematode orthologs of 21 proteins, which showed Alzheimer‐specific enrichment in tau‐containing aggregates, were assessed for aggregation‐promoting roles in C. elegans by RNA‐interference ‘knockdown’. Fifteen knockdowns (71%) rescued paralysis of worms expressing muscle Aβ, and 12 (57%) rescued chemotaxis disrupted by neuronal Aβ expression. Proteins identified in compact human aggregates, bound by antibody to total tau, were thus shown to play causal roles in aggregation based on nematode models triggered by Aβ1–42. These observations imply shared mechanisms driving both types of aggregation, and/or aggregate‐mediated cross‐talk between tau and Aβ. Knowledge of protein components that promote protein accrual in diverse aggregate types implicates common mechanisms and identifies novel targets for drug intervention.

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Section: Discussionmentioning

confidence: 99%

Proteins that mediate protein aggregation and cytotoxicity distinguish Alzheimer's hippocampus from normal controls

et al. 2016

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“…The carbohydrate metabolism-related proteins showed increased protein level in CCH rats. Among them, the glucose transport regulator astrocytic phosphoprotein PEA-15 (PEA-15) protein may play a protective role in AD (Ahn et al, 2014) and is able to bind to MAP2K1. MAP2K1 phosphorylation drives cytoplasmic accumulation of heterogeneous nuclear ribonucleoprotein K (HNRPK or HNRNPK) synaptic transmission and spine development regulator protein (Habelhah et al, 2001), whose expression pattern is also correlated with AD progression (Liang et al, 2012).…”

Section: Relationships Of Chronic Cerebral Hypoperfusion Altered Synamentioning

confidence: 99%

Chronic Cerebral Hypoperfusion Induced Synaptic Proteome Changes in the rat Cerebral Cortex

et al. 2017

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Chronic cerebral hypoperfusion (CCH) evokes mild cognitive impairment (MCI) and contributes to the progression of vascular dementia and Alzheimer's disease (AD). How CCH 2 induces these neurodegenerative processes that may spread along the synaptic network and whether they are detectable at the synaptic proteome level of the cerebral cortex remains to be established.In the present study, we report the synaptic protein changes in the cerebral cortex after stepwise bilateral common carotid artery occlusion (BCCAO) induced CCH in the rat. The occlusions were confirmed with Magnetic Resonance Angiography 5 weeks after the surgery.Synaptosome fractions were prepared using sucrose gradient centrifugation from cerebral cortex dissected 7 weeks after the occlusion. The synaptic protein differences between the sham operated and CCH groups were analysed with label free nanoUHPLC-MS/MS.

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“…Therefore, in recent years, fusion expression strategy of Pep-1 and cargo peptides or proteins (such as SOD, FK506BP, Heme oxygenase-1, Paraoxonase 1, PEA-15) has been widely explored by many researchers, and the results suggested that fusion expression with Pep-1 could obtain pleasing cell-permeable efficiency in cells in vitro, and penetrate easily even the blood-brain barrier in vivo. [28][29][30][31][32][33] Similarly, in this study, fusion of Pep-1 and hEGF could not only ensure the high expression level of the recombinant protein in E. coli, but also endue the protein with high transmembrane capability in Cos-7 fibroblasts.…”

Section: Discussionmentioning

confidence: 83%

Fusion with pep-1, a cell-penetrating peptide, enhances the transmembrane ability of human epidermal growth factor

Luo

Wang

et al. 2016

Bioscience, Biotechnology, and Biochemistry

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Administration of macromolecule compositions in medicine and cosmetics always exhibited low bioavailability due to the limitation of transmembrane transport. Here, human epidermal growth factor (hEGF) was fused with glutathione S-transferase (GST) and Pep-1, the first commercial cell-penetrating peptide, in Escherichia coli. The fusion protein was firstly purified with the affinity chromatography, and then the GST tag was released by TEV protease. Final purification was achieved by the ion exchange chromatography. The biological activities and the transmembrane ability of the obtained products were determined using scratch wound-healing assay, MTT analysis, and immunofluorescence assay. The results showed that both rhEGF and Pep-1-fused hEGF were soluble expressed in E. coli. The fusion of Pep-1 could markedly increase the transmembrane ability of EGF, whereas it did not interfere with the growth-stimulating and migration-promoting functions of hEGF on fibroblasts. This research provided a novel strategy for the transmembrane transport of protein-derived cosmetics or drugs.

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PEP-1-PEA-15 protects against toxin-induced neuronal damage in a mouse model of Parkinson's disease

Cited by 17 publications

References 66 publications

Proteins that mediate protein aggregation and cytotoxicity distinguish Alzheimer's hippocampus from normal controls

Proteins that mediate protein aggregation and cytotoxicity distinguish Alzheimer's hippocampus from normal controls

Chronic Cerebral Hypoperfusion Induced Synaptic Proteome Changes in the rat Cerebral Cortex

Fusion with pep-1, a cell-penetrating peptide, enhances the transmembrane ability of human epidermal growth factor

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