Evidence map›Paper›PMID 41518395›Full record

ArticleApoptosis : an international journal on programmed cell death2026

HSPA8 lactylation attenuates neuronal pyroptosis via E3 ligase-mediated NLRP3 degradation after ischemic stroke.

Jing Fu, Liang Yu, Nengwei Yu, Ping Ni, Chaohui He, Qiao Chen, Suping Li, Fei Xu

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Article in Apoptosis : an international journal on programmed cell death, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Jing FuDepartment of Rehabilitation, Sichuan Provincial People's Hospital, school of medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.
Liang YuDepartment of Neurology, Sichuan Provincial People's Hospital, school of medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.
Nengwei YuDepartment of Neurology, Sichuan Provincial People's Hospital, school of medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.
Ping NiDepartment of Neurology, Sichuan Provincial People's Hospital, school of medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.
Chaohui HeDepartment of Neurology, Sichuan Provincial People's Hospital, school of medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China.
Qiao ChenSchool of Medical and Life Sciences, Chengdu University of T.C.M, 610075, Chengdu, China.
Suping LiDepartment of Neurology, Sichuan Provincial People's Hospital, school of medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China. lisuping1900@163.com.
Fei XuDepartment of Neurology, Sichuan Provincial People's Hospital, school of medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China. 476627450@qq.com.

Funding

Heath Commission of Sichuan Province, China 24YWYL03Sichuan Provincial Administration of Traditional Chinese Medicine, China 2024MS513the Natural Science Foundation of Sichuan Province, Chinathe Natural Science Foundation of Sichuan Province, China 2025ZNSFSC0776
6 · The paper itself

Abstract

backgroundPyroptosis contributes significantly to neuronal death following ischemic stroke. This study investigated whether lactylation of heat shock protein family A member 8 (HSPA8) modulates neuronal pyroptosis after ischemic/reperfusion injury. RESEARCH DESIGN AND

methodsBoth in vitro oxygen-glucose deprivation/reperfusion (OGD/R) models and in vivo transient middle cerebral artery occlusion (tMCAO) mouse models were established to assess the functional significance of HSPA8 lactylation at lysine 524 (K524).

resultsHSPA8 expression and lactylation increased following ischemic/reperfusion injury both in vitro and in vivo. K524 was the predominant lactylation site, regulated by p300 acetyltransferase and histone deacetylases. The lactylation-mimetic K524Q mutant significantly reduced pyroptosis markers (NLRP3, GSDMD, cleaved caspase-1) and pyroptotic cell death compared to wild-type or K524R mutant. In tMCAO mice, neuronal expression of HSPA8-K524Q reduced infarct volume and suppressed pyroptosis more effectively than K524R. Mechanistically, HSPA8 lactylation at K524 enhanced its interaction with the E3 ubiquitin ligases PARK2 and ARIH2, promoting NLRP3 ubiquitination and degradation.

conclusionsHSPA8 lactylation at K524 is a critical regulator of neuronal pyroptosis and ischemic brain injury. This modification facilitates E3 ligase-mediated NLRP3 degradation and suppression of inflammasome activation. Targeting protein lactylation pathways may offer a promising therapeutic strategy for neuroprotection in ischemic stroke.

Indexed as

Ischemic StrokeNeuronsNLR Family, Pyrin Domain-Containing 3 ProteinPyroptosisUbiquitin-Protein LigasesAnimalsBrain IschemiaDisease Models, AnimalHSC70 Heat-Shock ProteinsHumansInfarction, Middle Cerebral ArteryMaleMiceMice, Inbred C57BLProteolysisReperfusion InjuryHSC70 Heat-Shock ProteinsHspa8 protein, mouseNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseUbiquitin-Protein LigasesHSPA8Ischemic strokeLactylationNLRP3Proteasomal degradationPyroptosis

Identifiers

PMID41518395

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.