Elamipretide Attenuates Pyroptosis and Perioperative Neurocognitive Disorders in Aged Mice.

Zuo Y, Yin L, Cheng X, Li J, Wu H, Liu X, Gu E, Wu J

Frontiers in cellular neuroscience13 Aug 2020Cited by 38 (Europe PMC)

PMID32903868PMCIDPMC7439217DOI10.3389/fncel.2020.00251PepBankPUB-32903868

Summary

Pyroptosis is a recently characterized inflammatory form of programmed cell death that is thought to be involved in the pathogenesis of perioperative neurocognitive disorders (PND). Elamipretide (SS-31), a mitochondrial-targeted peptide with multiple pharmacological properties, including anti-inflammatory activity, has been demonstrated to protect against many neurological diseases. However, the effect of elamipretide on pyroptosis in PND has not been studied. We established an animal model of PND by performing an exploratory laparotomy on mice under isoflurane anesthesia and examined the effects of elamipretide on cognitive function, synaptic integrity, neuroinflammation, mitochondrial function, and signaling controlling pyroptosis. Our results showed that anesthesia and surgery caused mitochondrial dysfunction and abnormal morphology, activation of canonicalnod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome-caspase-1 dependent pyroptosis, and downregulation of synaptic integrity-related proteins in the hippocampus in aged mice, thus leading to learning and memory deficits in behavioral tests. Remarkably, treatment with the mitochondrial-targeted peptide elamipretide not only had protective effects against mitochondrial dysfunction but also attenuated surgery-induced pyroptosis and cognitive deficits. Our results provide a promising strategy for the treatment of PND involving mitochondrial dysfunction and pyroptosis.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

3 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Mechanism
In aged mice after anaesthesia and surgery, elamipretide protected against mitochondrial dysfunction.
In plain wordsIn aged mice after surgery, elamipretide protected against mitochondrial dysfunction.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseSurgery-induced mitochondrial dysfunction
Study
mousen: not reported in source
Perioperative neurocognitive disorder (laparotomy under isoflurane, aged mice)
Outcome group
Mitochondrial function · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Remarkably, treatment with the mitochondrial-targeted peptide elamipretide not only had protective effects against mitochondrial dysfunction but also attenuated surgery-induced pyroptosis and cognitive deficits.
1 context sentence(design, population, supporting numbers)
Summary · context
We established an animal model of PND by performing an exploratory laparotomy on mice under isoflurane anesthesia and examined the effects of elamipretide on cognitive function, synaptic integrity, neuroinflammation, mitochondrial function, and signaling controlling pyroptosis.
Show in the study text Report a problemFND-3290386801
02AnimalAnimal study (in vivo)Mechanism
In aged mice after anaesthesia and surgery, elamipretide attenuated pyroptosis.
In plain wordsIn aged mice after surgery, elamipretide reduced a form of inflammatory cell death called pyroptosis.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseSurgery-induced pyroptosis
Study
mousen: not reported in source
Perioperative neurocognitive disorder (laparotomy under isoflurane, aged mice)
Outcome group
Inflammation markers · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Remarkably, treatment with the mitochondrial-targeted peptide elamipretide not only had protective effects against mitochondrial dysfunction but also attenuated surgery-induced pyroptosis and cognitive deficits.
1 context sentence(design, population, supporting numbers)
Summary · context
We established an animal model of PND by performing an exploratory laparotomy on mice under isoflurane anesthesia and examined the effects of elamipretide on cognitive function, synaptic integrity, neuroinflammation, mitochondrial function, and signaling controlling pyroptosis.
Show in the study text Report a problemFND-3290386802
03AnimalAnimal study (in vivo)Efficacy outcome
In aged mice after anaesthesia and surgery, elamipretide attenuated cognitive deficits.
In plain wordsIn aged mice after surgery, elamipretide reduced learning and memory problems.
Peptide
Elamipretide (SS-31)
Outcome
DecreaseSurgery-induced cognitive deficits
Study
mousen: not reported in source
Perioperative neurocognitive disorder (laparotomy under isoflurane, aged mice)
Outcome group
Cognition and memory · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Remarkably, treatment with the mitochondrial-targeted peptide elamipretide not only had protective effects against mitochondrial dysfunction but also attenuated surgery-induced pyroptosis and cognitive deficits.
1 context sentence(design, population, supporting numbers)
Summary · context
We established an animal model of PND by performing an exploratory laparotomy on mice under isoflurane anesthesia and examined the effects of elamipretide on cognitive function, synaptic integrity, neuroinflammation, mitochondrial function, and signaling controlling pyroptosis.
Show in the study text Report a problemFND-3290386803

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

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Version 2Current
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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