The neuroprotective and neurorescue effects of carbamylated erythropoietin Fc fusion protein (CEPO-Fc) in a rat model of Parkinson’s disease

Tayra, Judith Thomas; Kameda, Masahiro; Yasuhara, Takao; Agari, Takashi; Kadota, Toshikazu; Wang, Feifei; Kikuchi, Yoichiro; Liang, Hanbai; Shinko, Aiko; Wakamori, Takaaki; Vcelar, Brigitta; McCarley, Robert W.; Date, Isao

doi:10.1016/j.brainres.2013.01.042

Cited by 29 publications

(13 citation statements)

References 75 publications

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“…The EPO neuroprotective and anti-inflammatory effects are very well known and supported by a large body of literature, showing that in vivo administration of EPO promotes recovery of function after central nervous system lesions (Gorio et al., 2002; Brines and Cerami, 2008). Also in rat models of PD, it has been shown that the administration of rhEPO or EPO analogs had neuroprotective and neuro-rescue effects (Thomas et al., 2013; Jia et al., 2014; Erbaş et al., 2015). Therefore, it is conceivable that the release of such a neuroprotective factor by Er-NPCs may also have a favorable impact on the striatum dopaminergic functions, and consequently, on behavioral recovery.…”

Section: Discussionmentioning

confidence: 99%

Grafted Neural Precursors Integrate Into Mouse Striatum, Differentiate and Promote Recovery of Function Through Release of Erythropoietin in MPTP-Treated Mice

et al. 2016

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Erythropoietin-releasing neural precursor cells (Er-NPCs) are a subclass of subventricular zone-derived neural progenitors, capable of surviving for 6 hr after death of donor. They present higher neural differentiation. Here, Er-NPCs were studied in animal model of Parkinson’s disease. Dopaminergic degeneration was caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intraperitoneal administration in C57BL/6 mice. The loss of function was evaluated by specific behavioral tests. Er-NPCs (2.5 × 105) expressing the green fluorescent protein were administered by stereotaxic injection unilaterally in the left striatum. At the end of observational research period (2 weeks), most of the transplanted Er-NPCs were located in the striatum, while several had migrated ventrally and caudally from the injection site, up to ipsilateral and contralateral substantia nigra. Most of transplanted cells had differentiated into dopaminergic, cholinergic, or GABAergic neurons. Er-NPCs administration also promoted a rapid functional improvement that was already evident at the third day after cells administration. This was accompanied by enhanced survival of nigral neurons. These effects were likely promoted by Er-NPCs-released erythropoietin (EPO), since the injection of Er-NPCs in association with anti-EPO or anti-EPOR antibodies had completely neutralized the recovery of function. In addition, intrastriatal administration of recombinant EPO mimics the effects of Er-NPCs. We suggest that Er-NPCs, and cells with similar properties, may represent good candidates for cellular therapy in neurodegenerative disorders of this kind.

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Section: Discussionmentioning

confidence: 99%

Grafted Neural Precursors Integrate Into Mouse Striatum, Differentiate and Promote Recovery of Function Through Release of Erythropoietin in MPTP-Treated Mice

et al. 2016

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“…Surprisingly, the combined therapy significantly reduced mossy fiber sprouting, compared to other groups [10]. Furthermore, our recent data suggest robust neuroprotective effects, but without hematopoietic consequences, by carbamylated EPO Fc fusion protein in a Parkinson’s disease model [49]. We envision that this protein may be a new therapeutic agent for epilepsy.…”

Section: Basic Research and Clinical Application For Epilepsymentioning

confidence: 93%

Regenerative Medicine for Epilepsy: From Basic Research to Clinical Application

Yasuhara

Agari

Kameda

et al. 2013

IJMS

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Epilepsy is a chronic neurological disorder, which presents with various forms of seizures. Traditional treatments, including medication using antiepileptic drugs, remain the treatment of choice for epilepsy. Recent development in surgical techniques and approaches has improved treatment outcomes. However, several epileptic patients still suffer from intractable seizures despite the advent of the multimodality of therapies. In this article, we initially provide an overview of clinical presentation of epilepsy then describe clinically relevant animal models of epilepsy. Subsequently, we discuss the concepts of regenerative medicine including cell therapy, neuroprotective agents, and electrical stimulation, which are reviewed within the context of our data.

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“…В дальнейшем на различных моделях поражений головного и спинного мозга было подтверждено, что нейропротективное действие СЕРО также связано с его противовоспалительным и противоапоптозным эффектом: травматическое повреждение мозга [32], множественный ишемический инсульт, частичная перерезка спинного мозга [33], повреждение спинного мозга при ишемии/реперфузии [34] и фокальная ишемия головного мозга [33,35]. В относительно недавних исследованиях показан нейропротективный эффект СЕРО на моделях таких заболеваний ЦНС, как болезнь Альцгеймера [36], болезнь Паркинсона [37] и перивентрикулярная лейкомаляция [38].…”

Section: модификации эритропоэтина с селективным тканезащитным эффектомunclassified

“…Как и Эпо, Epotris проникает через ГЭБ, ослабляет нейротоксические эффекты каината, однако не стимулирует эритропоэз. В литературе присутствует информация об исследованиях пептидного аналога Эпо Epopeptide-ab, представляющего собой последовательность из 17 аминокислот (AEHCSLNENITVPDTKV), соответствующую области AB-петли Эпо (последовательность аминокислот [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47], который обладает активностью, сходной с целым белком. Нейропротективный эффект Epopeptide-ab подтвержден в опытах in vivo на модели ишемического повреждения нейронов [59].…”

Section: пептидные производные эритропоэтина обладающие тканезащитныunclassified

Pathogenic substantiation of application of erythropoietin modified forms and peptide analogues as cytotprotectors

Ivanov¹,

Никифоров²,

Венгерович

et al. 2020

Pharmacy Formulas

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Provides a review of the evidence from experimental and clinical studies on the blood-forming and non-blood-forming tissue protective effects of erythropoietin. Information on its side effects (stimulation of tumor growth, autoimmune reactions, arterial hypertension, etc.), limiting the clinical use as a cytoprotector, is summarized. Well-known modifications of the erythropoietin molecule with a tissue protective effect are considered, in particular, desialylated (asialoEPO), carboxylated (CEPO) and glutaraldehyde (GEPO) cytokine analogues. The results of biomedical studies describing the tissue protective effects of these compounds, as well as possible mechanisms of their receptor action, are presented. The article discusses the main short-chain erythropoietin mimetics that reproduce individual active regions of cytokine amino acid sequence and contain from 11 to 25 amino acids: Helix B, ARA290, Eportis, Epopeptide-ab, MK-X, Epobis, NL100. The biochemical mechanisms of cytoprotective action of erythropoietin and its derivatives are considered, including binding to the heterodimeric receptor of non-blood-forming tissues and activation of intracellular signaling molecules possessing properties of apopotosis inhibitors. It was noted that the tissue protective effect of erythropoietin in vivo is observed in hemostimulating doses and is accompanied by side effects. At the same time, the use of modified forms of erythropoietin and its short-chain peptide analogues, which have a high affinity for the isoform of the erythropoietin receptor of non-blood-forming tissues and do not have hematopoietic properties, allows avoiding the development of side effects and reducing effective doses by 10-20 times.

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The neuroprotective and neurorescue effects of carbamylated erythropoietin Fc fusion protein (CEPO-Fc) in a rat model of Parkinson’s disease

Cited by 29 publications

References 75 publications

Grafted Neural Precursors Integrate Into Mouse Striatum, Differentiate and Promote Recovery of Function Through Release of Erythropoietin in MPTP-Treated Mice

Grafted Neural Precursors Integrate Into Mouse Striatum, Differentiate and Promote Recovery of Function Through Release of Erythropoietin in MPTP-Treated Mice

Regenerative Medicine for Epilepsy: From Basic Research to Clinical Application

Pathogenic substantiation of application of erythropoietin modified forms and peptide analogues as cytotprotectors

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