Enkephalins and ACTH in the mammalian nervous system

Duque-Díaz, Ewing; Álvarez-Ojeda, Olga Mercedes; Coveñas, Rafael

doi:10.1016/bs.vh.2019.05.001

Cited by 14 publications

(10 citation statements)

References 166 publications

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“…Besides the primary endogenous ligands of δ-opioid receptors, the enkephalins, other opioids bind them as well. The main roles of enkephalins in hypoxia-relevant functions are the modulation of neurotransmitter release, calcium regulation, neuroinflammation, neuroprotection, energy metabolism, angiogenesis and others [ 131 ]. Their anatomical distribution, furthermore, may indicate a role of enkephalins in the regulation of (systemic) respiration [ 132 ], and thus also a potential involvement in adaptations to hypoxia on a systemic level.…”

Section: Overlapping Molecular Pathways Of Hypoxic and Chemical Comentioning

confidence: 99%

A Rationale for Hypoxic and Chemical Conditioning in Huntington’s Disease

Burtscher

Maglione

Pardo

et al. 2021

IJMS

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Neurodegenerative diseases are characterized by adverse cellular environments and pathological alterations causing neurodegeneration in distinct brain regions. This development is triggered or facilitated by conditions such as hypoxia, ischemia or inflammation and is associated with disruptions of fundamental cellular functions, including metabolic and ion homeostasis. Targeting intracellular downstream consequences to specifically reverse these pathological changes proved difficult to translate to clinical settings. Here, we discuss the potential of more holistic approaches with the purpose to re-establish a healthy cellular environment and to promote cellular resilience. We review the involvement of important molecular pathways (e.g., the sphingosine, δ-opioid receptor or N-Methyl-D-aspartate (NMDA) receptor pathways) in neuroprotective hypoxic conditioning effects and how these pathways can be targeted for chemical conditioning. Despite the present scarcity of knowledge on the efficacy of such approaches in neurodegeneration, the specific characteristics of Huntington’s disease may make it particularly amenable for such conditioning techniques. Not only do classical features of neurodegenerative diseases like mitochondrial dysfunction, oxidative stress and inflammation support this assumption, but also specific Huntington’s disease characteristics: a relatively young age of neurodegeneration, molecular overlap of related pathologies with hypoxic adaptations and sensitivity to brain hypoxia. The aim of this review is to discuss several molecular pathways in relation to hypoxic adaptations that have potential as drug targets in neurodegenerative diseases. We will extract the relevance for Huntington’s disease from this knowledge base.

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Section: Overlapping Molecular Pathways Of Hypoxic and Chemical Comentioning

confidence: 99%

A Rationale for Hypoxic and Chemical Conditioning in Huntington’s Disease

Burtscher

Maglione

Pardo

et al. 2021

IJMS

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“…For this reason, the same precursor may result in different opioid peptides ( Figure 1 ) [ 8 , 9 ]. It is known that the Tyr and Phe amino acids of the opioid motif are essential for binding the opioid receptor, while the Gly pair acts as a spacer [ 10 , 11 ]. These peptides undergo post-translational, cell-specific modifications, such as acetylation, glycosylation, phosphorylation, and methylation.…”

Section: Introductionmentioning

confidence: 99%

“…Enkephalins are degraded through the hydrolysis of the pentapeptide at the Tyr–Gly bond. Then, the molecules are reduced into shorter peptides (from two to four amino acids) by enkephalinases and aminopeptidases [ 10 ]. Since these small peptides have a short half-life both in vivo and in vitro, researchers also use synthetic forms of enkephalins, which are much more stable.…”

Section: Introductionmentioning

confidence: 99%

Endogenous Opioids and Their Role in Stem Cell Biology and Tissue Rescue

Petrocelli

Pampanella

Abruzzo

et al. 2022

IJMS

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Opioids are considered the oldest drugs known by humans and have been used for sedation and pain relief for several centuries. Nowadays, endogenous opioid peptides are divided into four families: enkephalins, dynorphins, endorphins, and nociceptin/orphanin FQ. They exert their action through the opioid receptors (ORs), transmembrane proteins belonging to the super-family of G-protein-coupled receptors, and are expressed throughout the body; the receptors are the δ opioid receptor (DOR), μ opioid receptor (MOR), κ opioid receptor (KOR), and nociceptin/orphanin FQ receptor (NOP). Endogenous opioids are mainly studied in the central nervous system (CNS), but their role has been investigated in other organs, both in physiological and in pathological conditions. Here, we revise their role in stem cell (SC) biology, since these cells are a subject of great scientific interest due to their peculiar features and their involvement in cell-based therapies in regenerative medicine. In particular, we focus on endogenous opioids’ ability to modulate SC proliferation, stress response (to oxidative stress, starvation, or damage following ischemia–reperfusion), and differentiation towards different lineages, such as neurogenesis, vasculogenesis, and cardiogenesis.

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“…The classical receptors are mu (MORs, mainly expressed in the central nervous system (CNS), delta (DORs, expressed in the CNS and spinal cord), and kappa (KORs, expressed primarily in the spinal cord); and the non-classical receptors are the opioid growth factor receptor (OGFr) that are expressed in multiple targets organ [ 1 , 2 , 3 ]. The binding to classical and non-classical opioid receptors produces relevant biologic functions such as analgesia, hypoxia, limbic system modulation, neuroprotection, cardiovascular and respiration control, embryonic development, and cell division and growth [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Opioids and Ocular Surface Pathology: A Literature Review of New Treatments Horizons

García-López

Gómez-Huertas

Sánchez‐González

et al. 2022

JCM

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This review discusses the role of opioids in the corneal surface and the different pathways and therapeutic methods of management. A literature review was performed using PubMed database. For the database search, the main searching words “opioid” and “topical opioid treatment” were used with the descriptors “cornea”, “ocular surface”, “neuropathic corneal pain”, “corneal sensitivity” and “naltrexone”; original scientific articles and reviews were included to achieve the purpose of the review. The endogenous opioid system has relevant functions in the organism, and in daily use, opioids are used as painkillers. However, these drugs may be employed for other indications as opioid pathways have a wide spectrum. The corneal surface for topical treatment is easily accessible, hence sparing the side effects of systemic opioids. Instillation of opioid antagonist substances, such as naltrexone, increases corneal healing rates and stimulates the division of corneal epithelium cells without deleterious effects. The natural modulation of endogenous opioids controls different forms of pain, including inflammatory and neuropathic pain, both in the ocular surface and in the central nervous system. There are diverse methods in controlling pain using opioids, especially in refractory forms. This review attempts to collect the literature about corneal surface and opioid pathways to provide an overview image and a possible direction of the news treatments.

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Enkephalins and ACTH in the mammalian nervous system

Cited by 14 publications

References 166 publications

A Rationale for Hypoxic and Chemical Conditioning in Huntington’s Disease

A Rationale for Hypoxic and Chemical Conditioning in Huntington’s Disease

Endogenous Opioids and Their Role in Stem Cell Biology and Tissue Rescue

Opioids and Ocular Surface Pathology: A Literature Review of New Treatments Horizons

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