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Proteomic Exploration of Paraoxonase 1 Function in Health and Disease

cris.virtual.author-orcid0000-0001-5845-4409
cris.virtualsource.author-orcid4dde7a12-8c22-4e89-9d57-7c74b050ccc5
dc.abstract.enHigh-density lipoprotein (HDL) exhibits cardio- and neuro-protective properties, which are thought to be promoted by paraoxonase 1 (PON1), a hydrolytic enzyme associated with an HDL subfraction also enriched with an anticoagulant protein (PROS1) and amyloid beta-transport protein clusterin (CLU, APOJ). Reduced levels of PON1 activity, characterized biochemically by elevated levels of homocysteine (Hcy)-thiolactone, oxidized lipids, and proteins modified by these metabolites in humans and mice, are associated with pathological abnormalities affecting the cardiovascular system (atherothrombosis) and the central nervous system (cognitive impairment, Alzheimer’s disease). The molecular bases of these abnormalities have been largely unknown. Proteomic and metabolic studies over the past decade have significantly contributed to our understanding of PON1 function and the mechanisms by which PON1 deficiency can lead to disease. Recent studies discussed in this review highlight the involvement of dysregulated proteostasis in the pro-oxidative, pro-atherothrombotic, and pro-amyloidogenic phenotypes associated with low PON1 activity.
dc.affiliationWydział Rolnictwa, Ogrodnictwa i Biotechnologii
dc.affiliation.instituteKatedra Biochemii i Biotechnologii
dc.contributor.authorJakubowski, Hieronim
dc.date.access2025-04-09
dc.date.accessioned2025-08-26T07:11:55Z
dc.date.available2025-08-26T07:11:55Z
dc.date.copyright2023-04-24
dc.date.issued2023
dc.description.abstract<jats:p>High-density lipoprotein (HDL) exhibits cardio- and neuro-protective properties, which are thought to be promoted by paraoxonase 1 (PON1), a hydrolytic enzyme associated with an HDL subfraction also enriched with an anticoagulant protein (PROS1) and amyloid beta-transport protein clusterin (CLU, APOJ). Reduced levels of PON1 activity, characterized biochemically by elevated levels of homocysteine (Hcy)-thiolactone, oxidized lipids, and proteins modified by these metabolites in humans and mice, are associated with pathological abnormalities affecting the cardiovascular system (atherothrombosis) and the central nervous system (cognitive impairment, Alzheimer’s disease). The molecular bases of these abnormalities have been largely unknown. Proteomic and metabolic studies over the past decade have significantly contributed to our understanding of PON1 function and the mechanisms by which PON1 deficiency can lead to disease. Recent studies discussed in this review highlight the involvement of dysregulated proteostasis in the pro-oxidative, pro-atherothrombotic, and pro-amyloidogenic phenotypes associated with low PON1 activity.</jats:p>
dc.description.accesstimeat_publication
dc.description.bibliographyil., bibliogr.
dc.description.financepublication_nocost
dc.description.financecost0,00
dc.description.if4,9
dc.description.number9
dc.description.points140
dc.description.versionfinal_published
dc.description.volume24
dc.identifier.doi10.3390/ijms24097764
dc.identifier.eissn1422-0067
dc.identifier.issn1661-6596
dc.identifier.urihttps://sciencerep.up.poznan.pl/handle/item/4349
dc.identifier.weblinkhttps://www.mdpi.com/1422-0067/24/9/7764
dc.languageen
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.relation.pagesart. 7764
dc.rightsCC-BY
dc.sciencecloudnosend
dc.share.typeOPEN_JOURNAL
dc.subject.enparaoxonase 1
dc.subject.enhomocysteine
dc.subject.enproteostasis
dc.subject.enoxidative stress
dc.subject.encardiovascular disease
dc.subject.enAlzheimer’s disease
dc.subtypeReviewArticle
dc.titleProteomic Exploration of Paraoxonase 1 Function in Health and Disease
dc.title.volumeSpecial Issue Latest Review Papers in Molecular and Cellular Biology 2023
dc.typeJournalArticle
dspace.entity.typePublication
oaire.citation.issue9
oaire.citation.volume24