From neurogenesis to neuroprotection in the epilepsy: signalling by erythropoietin

Castañeda‐Arellano, Rolando; Beas‐Zárate, Carlos; Feria‐Velasco, Alfredo; Bitar-Alatorre, Emilio W; Rivera-Cervantes, M.C.

doi:10.2741/4295

Cited by 24 publications

(14 citation statements)

References 51 publications

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“…EPO is then processed with the removal of a carboxy-terminal arginine 166 in the mature human and recombinant human EPO (rhEPO). A protein of 165 amino acids with a molecular weight of 30.4 kDa is subsequently generated (65–68). EPO, an erythropoiesis-stimulating agents, is approved for the treatment of anemia that results from chronic kidney failure, human immunodeficiency virus, and chemotherapy.…”

Section: Trpv1 and Erythropoietinmentioning

confidence: 99%

Warming Up to New Possibilities with the Capsaicin Receptor TRPV1: mTOR, AMPK, and Erythropoietin

Maiese

2017

CNR

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BACKGROUND Transient receptor potential (TRP) channels are a superfamily of ion channels termed after the trp gene in Drosophila that are diverse in structure and control a wide range of biological functions including cell development and growth, thermal regulation, and vascular physiology. Of significant interest is the transient receptor potential cation channel subfamily V member 1 (TRPV1) receptor, also known as the capsaicin receptor and the vanilloid receptor 1, that is a non-selective cation channel sensitive to a host of external stimuli including capsaicin and camphor, venoms, acid/basic pH changes, and temperature. METHODS Given the multiple modalities that TRPV1 receptors impact in the body, we examined and discussed the role of these receptors in vasomotor control, metabolic disorders, cellular injury, oxidative stress, apoptosis, autophagy, and neurodegenerative disorders and their overlap with other signal transduction pathways that impact trophic factors. RESULTS Surprisingly, TRPV1 receptors do not rely entirely upon calcium signaling to affect cellular biology, but also have a close relationship with the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), and protein kinase B (Akt) that have roles in pain sensitivity, stem cell development, cellular survival, and cellular metabolism. These pathways with TRPV1 converge in the signaling of growth factors with recent work highlighting a relationship with erythropoietin (EPO). Angiogenesis and endothelial tube formation controlled by EPO requires, in part, the activation of TRPV1 receptors in conjunction with Akt and AMPK pathways. CONCLUSIONS TRPV1 receptors could prove to become vital to target disorders of vascular origin and neurodegeneration. Broader and currently unrealized implementations for both EPO and TRPV1 receptors can be envisioned for for the development of novel therapeutic strategies in multiple systems of the body.

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Section: Trpv1 and Erythropoietinmentioning

confidence: 99%

Warming Up to New Possibilities with the Capsaicin Receptor TRPV1: mTOR, AMPK, and Erythropoietin

Maiese

2017

CNR

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“…During oxidative stress, FoxO may bind to β -catenin and prevent stem cell development similar to the previously described pathways with Wnt signaling [ 212 , 235 ]. Cellular mechanisms that utilize Wnt signaling such as EPO also control FoxO protein activity for stem cell growth [ 236 – 241 ]. EPO promotes erythroid progenitor cell development that requires the modulation of FoxO3a activity [ 46 , 172 , 242 , 243 ].…”

Section: Forkhead Transcription Factors Development Stem Cell Prmentioning

confidence: 99%

FoxO Proteins in the Nervous System

Maiese¹

2015

Analytical Cellular Pathology

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Acute as well as chronic disorders of the nervous system lead to significant morbidity and mortality for millions of individuals globally. Given the ability to govern stem cell proliferation and differentiated cell survival, mammalian forkhead transcription factors of the forkhead box class O (FoxO) are increasingly being identified as potential targets for disorders of the nervous system, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and auditory neuronal disease. FoxO proteins are present throughout the body, but they are selectively expressed in the nervous system and have diverse biological functions. The forkhead O class transcription factors interface with an array of signal transduction pathways that include protein kinase B (Akt), serum- and glucocorticoid-inducible protein kinase (SgK), IκB kinase (IKK), silent mating type information regulation 2 homolog 1 (S. cerevisiae) (SIRT1), growth factors, and Wnt signaling that can determine the activity and integrity of FoxO proteins. Ultimately, there exists a complex interplay between FoxO proteins and their signal transduction pathways that can significantly impact programmed cell death pathways of apoptosis and autophagy as well as the development of clinical strategies for the treatment of neurodegenerative disorders.

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“…Once generated as a protein, EPO is then processed and cleaved of a 27 amino acid hydrophobic secretory leader at the amino-terminal to result in a 166 amino acid peptide (127). A mature protein is subsequently formed with the removal of a carboxy-terminal arginine 166 in the mature human and recombinant human EPO (rhEPO) to generate a circulatory EPO protein of 165 amino acids with a molecular weight of 30.4. kDa (128–131) (Table 1). …”

Section: The Growth Factor and Cytokine Erythropoietinmentioning

confidence: 99%

Regeneration in the nervous system with erythropoietin

Maiese¹

2016

Front Biosci

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Globally, greater than 30 million individuals are afflicted with disorders of the nervous system accompanied by tens of thousands of new cases annually with limited, if any, treatment options. Erythropoietin (EPO) offers an exciting and novel therapeutic strategy to address both acute and chronic neurodegenerative disorders. EPO governs a number of critical protective and regenerative mechanisms that can impact apoptotic and autophagic programmed cell death pathways through protein kinase B (Akt), sirtuins, mammalian forkhead transcription factors, and wingless signaling. Translation of the cytoprotective pathways of EPO into clinically effective treatments for some neurodegenerative disorders has been promising, but additional work is necessary. In particular, development of new treatments with erythropoiesis-stimulating agents such as EPO brings several important challenges that involve detrimental vascular outcomes and tumorigenesis. Future work that can effectively and safely harness the complexity of the signaling pathways of EPO will be vital for the fruitful treatment of disorders of the nervous system.

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From neurogenesis to neuroprotection in the epilepsy: signalling by erythropoietin

Cited by 24 publications

References 51 publications

Warming Up to New Possibilities with the Capsaicin Receptor TRPV1: mTOR, AMPK, and Erythropoietin

Warming Up to New Possibilities with the Capsaicin Receptor TRPV1: mTOR, AMPK, and Erythropoietin

FoxO Proteins in the Nervous System

Regeneration in the nervous system with erythropoietin

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