Regeneration in the nervous system with erythropoietin

Maiese, Kenneth

doi:10.2741/4408

Cited by 50 publications

(38 citation statements)

References 415 publications

(482 reference statements)

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“…The EPO gene is located on chromosome 7 and is a single copy in a 5.4 kb region of the genomic DNA (63). This gene encodes for a polypeptide chain protein that has initially 193 amino acids (64).…”

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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“…The N -linked glycosylation sites exist at aspartyl 24 , aspartyl 38 , and aspartyl 83 . The O -linked glycosylation site occurs at serine 126 (209). It is postulated that the N - and O -linked chains are for the production and secretion of the mature EPO (234).…”

Section: Erythropoietin and The Modulation Of Mtormentioning

confidence: 99%

“…Several cell survival pathways that EPO oversees are intimately tied to mTOR signaling (205–207, 209, 247, 253, 254). For stem cell development and the maturation of cells, EPO relies upon mTOR for the differentiation of neural precursor cells to achieve a neuronal phenotype (254).…”

Section: Erythropoietin and The Modulation Of Mtormentioning

confidence: 99%

Erythropoietin and mTOR: A “One-Two Punch” for Aging-Related Disorders Accompanied by Enhanced Life Expectancy

Maiese¹

2016

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Life expectancy continues to increase throughout the world, but is accompanied by a rise in the incidence of non-communicable diseases. As a result, the benefits of an increased lifespan can be limited by aging-related disorders that necessitate new directives for the development of effective and safe treatment modalities. With this objective, the mechanistic target of rapamycin (mTOR), a 289-kDa serine/threonine protein, and its related pathways of mTOR Complex 1 (mTORC1), mTOR Complex 2 (mTORC2), proline rich Akt substrate 40 kDa (PRAS40), AMP activated protein kinase (AMPK), Wnt signaling, and silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), have generated significant excitement for furthering novel therapies applicable to multiple systems of the body. Yet, the biological and clinical outcome of these pathways can be complex especially with oversight of cell death mechanisms that involve apoptosis and autophagy. Growth factors, and in particular erythropoietin (EPO), are one avenue under consideration to implement control over cell death pathways since EPO can offer potential treatment for multiple disease entities and is intimately dependent upon mTOR signaling. In experimental and clinical studies, EPO appears to have significant efficacy in treating several disorders including those involving the developing brain. However, in mature populations that are affected by aging-related disorders, the direction for the use of EPO to treat clinical disease is less clear that may be dependent upon a number of factors including the understanding of mTOR signaling. Continued focus upon the regulatory elements that control EPO and mTOR signaling could generate critical insights for targeting a broad range of clinical maladies.

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“…Such agents are fostering a high level of enthusiasm for further investigation. In particular, the cytokine and growth factor erythropoietin (EPO) is under active study for the treatment of TBI [31]. …”

Section: Erythropoietin and Traumatic Brain Injury: Translating Expermentioning

confidence: 99%

“…Overall, greater than sixty current or completed clinical trials are listed on the National Institutes of Health website ClinicalTrials.gov for nervous system disorders and EPO [31]. For disorders such as sporadic AD, increased expression of the EPO receptor in temporal cortical and hippocampal astrocytes has been observed and considered to be an early neuroprotective pathway [99].…”

Section: Erythropoietin and Traumatic Brain Injury: Translating Expermentioning

confidence: 99%

Charting a course for erythropoietin in traumatic brain injury

Maiese¹

2016

J Transl Sci

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Traumatic brain injury (TBI) is a severe public health problem that impacts more than four million individuals in the United States alone and is increasing in incidence on a global scale. Importantly, TBI can result in acute as well as chronic impairments for the nervous system leaving individuals with chronic disability and in instances of severe trauma, death becomes the ultimate outcome. In light of the significant negative health consequences of TBI, multiple therapeutic strategies are under investigation, but those focusing upon the cytokine and growth factor erythropoietin (EPO) have generated a great degree of enthusiasm. EPO can control cell death pathways tied to apoptosis and autophagy as well oversees processes that affect cellular longevity and aging. In vitro studies and experimental animal models of TBI have shown that EPO can restore axonal integrity, promote cellular proliferation, reduce brain edema, and preserve cellular energy homeostasis and mitochondrial function. Clinical studies for neurodegenerative disorders that involve loss of cognition or developmental brain injury support a positive role for EPO to prevent or reduce injury in the nervous system. However, recent clinical trials with EPO and TBI have not produced such clear conclusions. Further clinical studies are warranted to address the potential efficacy of EPO during TBI, the concerns with the onset, extent, and duration of EPO therapeutic strategies, and to focus upon the specific downstream pathways controlled by EPO such as protein kinase B (Akt), mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), sirtuins, wingless pathways, and forkhead transcription factors for improved precision against the detrimental effects of TBI. KeywordsAkt; Alzheimer's disease; apoptosis; autophagy; erythropoietin; forkhead; mTOR; Parkinson's disease; neurodegeneration; programmed cell death; sirtuins; traumatic brain injury; Wnt Erythropoietin and traumatic brain injury: Translating experimental success into clinical efficacyIn more than 30 million individuals throughout the world, both acute and chronic neurodegenerative disorders can result in significant disability as well as eventual death [1,2]. Chronic neurodegenerative diseases, such as Parkinson's disease (PD) [3,4], can affect approximately 4 percent of individuals over the age of sixty. In addition, the number ofThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. For the sporadic form of AD, approximately 10 percent of the global population over the age of sixty-five is affected [3,5]. Over the next two decades, it is estimated that the number of those suffering from AD will increase significantly to more than 30 million individuals [6][7][8]. HHS Public AccessFor acute neurodegenerative injury, disorders such as stroke can impact almost 800,000 individuals every year with a...

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Regeneration in the nervous system with erythropoietin

Cited by 50 publications

References 415 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

Erythropoietin and mTOR: A “One-Two Punch” for Aging-Related Disorders Accompanied by Enhanced Life Expectancy

Charting a course for erythropoietin in traumatic brain injury

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