Mitochondria-derived peptide is an effective target for treating streptozotocin induced painful diabetic neuropathy through induction of activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1alpha -mediated mitochondrial biogenesis.
Mol Pain
; 20: 17448069241252654, 2024.
Article
in En
| MEDLINE
| ID: mdl-38658141
ABSTRACT
Painful Diabetic Neuropathy (PDN) is a common diabetes complication that frequently causes severe hyperalgesia and allodynia and presents treatment challenges. Mitochondrial-derived peptide (MOTS-c), a novel mitochondrial-derived peptide, has been shown to regulate glucose metabolism, insulin sensitivity, and inflammatory responses. This study aimed to evaluate the effects of MOTS-c in streptozocin (STZ)-induced PDN model and investigate the putative underlying mechanisms. We found that endogenous MOTS-c levels in plasma and spinal dorsal horn were significantly lower in STZ-treated mice than in control animals. Accordingly, MOTS-c treatment significantly improves STZ-induced weight loss, elevation of blood glucose, mechanical allodynia, and thermal hyperalgesia; however, these effects were blocked by dorsomorphin, an adenosine monophosphate-activated protein kinase (AMPK) inhibitor. In addition, MOTS-c treatment significantly enhanced AMPKα1/2 phosphorylation and PGC-1α expression in the lumbar spinal cord of PDN mice. Mechanistic studies indicated that MOTS-c significantly restored mitochondrial biogenesis, inhibited microglia activation, and decreased the production of pro-inflammatory factors, which contributed to the alleviation of pain. Moreover, MOTS-c decreased STZ-induced pain hypersensitivity in PDN mice by activating AMPK/PGC-1α signaling pathway. This provides the pharmacological and biological evidence for developing mitochondrial peptide-based therapeutic agents for PDN.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Organelle Biogenesis
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Streptozocin
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Diabetic Neuropathies
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Hyperalgesia
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Mitochondria
Limits:
Animals
Language:
En
Journal:
Mol Pain
Journal subject:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
/
PSICOFISIOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: