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Protein Quality Control and Integrated Stress Response Related to Pain...
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Protein Quality Control and Integrated Stress Response Related to Pain Disorders

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 6341

Special Issue Editor

Prof. Dr. Tomohiko Aoe

E-Mail Website
Guest Editor
Pain Center, Teikyo University Chiba Medical Center, Teikyo University, 3426-3 Anesaki, Ichihara City 299-0111, Chiba, Japan
Interests: cell biology; ER (endoplasmic reticulum) stress; chaperone; neuroscience; opioid; neurodegeneration; anesthetic action; chronic Pain
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Protein quality control ensures the intracellular transport of properly folded proteins to proper locations in the cell. Disturbance of this process leads to integrated stress response including the unfolded protein response in the endoplasmic reticulum and the heat shock response in the cytosol. Integrated stress response compensates against the accumulation of misfolded proteins due to extracellular insults such as oxidative stress and toxic substances as well as intrinsic conditions such as aging, malnutrition, and gene modifications. Integrated stress response involves intracellular signaling and various cellular interactions, often associated with pathogenic conditions.

Acute and chronic pain cause changes in the intracellular signal transduction system and affect cell–cell interactions. These changes may be correlated with protein quality control and stress response. This Special Issue focuses on protein quality control and integrated stress response related to acute and chronic pain disorders. Topics may include the pathophysiology of neuropathic pain, the neurotoxicity of general anesthesia, opioid tolerance, opioid misuse, pain disorders with neurodegenerative diseases, etc. We welcome the submission of review articles and original studies regarding basic cellular experiments, animal models, and human diseases.

Prof. Dr. Tomohiko Aoe
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • proteostasis
  • ER stress
  • UPR
  • heat shock response
  • HSP
  • chaperone
  • protein aggregation
  • analgesia
  • anesthesia
  • opioid

Published Papers (2 papers)

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Research

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15 pages, 2210 KiB  
Article
Pharmacological Chaperones Attenuate the Development of Opioid Tolerance
by Youta Okuyama, Hisayo Jin, Hiroshi Kokubun and Tomohiko Aoe
Int. J. Mol. Sci. 2020, 21(20), 7536; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21207536 - 13 Oct 2020
Cited by 4 | Viewed by 2178
Abstract
Opioids are potent analgesics widely used to control acute and chronic pain, but long-term use induces tolerance that reduces their effectiveness. Opioids such as morphine bind to mu opioid receptors (MORs), and several downstream signaling pathways are capable of inducing tolerance. We previously [...] Read more.
Opioids are potent analgesics widely used to control acute and chronic pain, but long-term use induces tolerance that reduces their effectiveness. Opioids such as morphine bind to mu opioid receptors (MORs), and several downstream signaling pathways are capable of inducing tolerance. We previously reported that signaling from the endoplasmic reticulum (ER) contributed to the development of morphine tolerance. Accumulation of misfolded proteins in the ER induced the unfolded protein response (UPR) that causes diverse pathological conditions. We examined the effects of pharmacological chaperones that alleviate ER stress on opioid tolerance development by assessing thermal nociception in mice. Pharmacological chaperones such as tauroursodeoxycholic acid and 4-phenylbutyrate suppressed the development of morphine tolerance and restored analgesia. Chaperones alone did not cause analgesia. Although morphine administration induced analgesia when glycogen synthase kinase 3β (GSK3β) was in an inactive state due to serine 9 phosphorylation, repeated morphine administration suppressed this phosphorylation event. Co-administration of chaperones maintained the inactive state of GSK3β. These results suggest that ER stress may facilitate morphine tolerance due to intracellular crosstalk between the UPR and MOR signaling. Pharmacological chaperones may be useful in the management of opioid misuse. Full article
(This article belongs to the Special Issue Protein Quality Control and Integrated Stress Response Related to Pain Disorders)
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Review

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17 pages, 2310 KiB  
Review
TRPV1 Channel: A Noxious Signal Transducer That Affects Mitochondrial Function
by Rebeca Juárez-Contreras, Karina Angélica Méndez-Reséndiz, Tamara Rosenbaum, Ricardo González-Ramírez and Sara Luz Morales-Lázaro
Int. J. Mol. Sci. 2020, 21(23), 8882; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21238882 - 24 Nov 2020
Cited by 21 | Viewed by 3690
Abstract
The Transient Receptor Vanilloid 1 (TRPV1) or capsaicin receptor is a nonselective cation channel, which is abundantly expressed in nociceptors. This channel is an important transducer of several noxious stimuli, having a pivotal role in pain development. Several TRPV1 studies have focused on [...] Read more.
The Transient Receptor Vanilloid 1 (TRPV1) or capsaicin receptor is a nonselective cation channel, which is abundantly expressed in nociceptors. This channel is an important transducer of several noxious stimuli, having a pivotal role in pain development. Several TRPV1 studies have focused on understanding its structure and function, as well as on the identification of compounds that regulate its activity. The intracellular roles of these channels have also been explored, highlighting TRPV1′s actions in the homeostasis of Ca2+ in organelles such as the mitochondria. These studies have evidenced how the activation of TRPV1 affects mitochondrial functions and how this organelle can regulate TRPV1-mediated nociception. The close relationship between this channel and mitochondria has been determined in neuronal and non-neuronal cells, demonstrating that TRPV1 activation strongly impacts on cell physiology. This review focuses on describing experimental evidence showing that TRPV1 influences mitochondrial function. Full article
(This article belongs to the Special Issue Protein Quality Control and Integrated Stress Response Related to Pain Disorders)
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