The Scaffold Protein PICK1 as a Target in Chronic Pain.
calcium permeable AMPAR
drug development
inflammatory pain
maladaptive plasticity
neuropathic pain
therapeutic peptides
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
07 04 2022
07 04 2022
Historique:
received:
08
03
2022
revised:
23
03
2022
accepted:
30
03
2022
entrez:
23
4
2022
pubmed:
24
4
2022
medline:
27
4
2022
Statut:
epublish
Résumé
Well-tolerated and effective drugs for treating chronic pain conditions are urgently needed. Most chronic pain patients are not effectively relieved from their pain and suffer from debilitating drug side effects. This has not only drastic negative consequences for the patients' quality of life, but also constitute an enormous burden on society. It is therefore of great interest to explore new potent targets for effective pain treatment with fewer side effects and without addiction liability. A critical component of chronic pain conditions is central sensitization, which involves the reorganization and strengthening of synaptic transmission within nociceptive pathways. Such changes are considered as maladaptive and depend on changes in the surface expression and signaling of AMPA-type glutamate receptors (AMPARs). The PDZ-domain scaffold protein PICK1 binds the AMPARs and has been suggested to play a key role in these maladaptive changes. In the present paper, we review the regulation of AMPARs by PICK1 and its relation to pain pathology. Moreover, we highlight other pain-relevant PICK1 interactions, and we evaluate various compounds that target PICK1 and have been successfully tested in pain models. Finally, we evaluate the potential on-target side effects of interfering with the action of PICK1 action in CNS and beyond. We conclude that PICK1 constitutes a valid drug target for the treatment of inflammatory and neuropathic pain conditions without the side effects and abuse liability associated with current pain medication.
Identifiants
pubmed: 35455935
pii: cells11081255
doi: 10.3390/cells11081255
pmc: PMC9031029
pii:
doi:
Substances chimiques
Carrier Proteins
0
Nuclear Proteins
0
PICk1 protein, human
0
Receptors, AMPA
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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