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Homocysteine Thiolactone Detoxifying Enzymes and Alzheimer’s Disease

cris.virtual.author-orcid0000-0001-5845-4409
cris.virtualsource.author-orcid4dde7a12-8c22-4e89-9d57-7c74b050ccc5
dc.abstract.enElevated levels of homocysteine (Hcy) and related metabolites are associated with Alzheimer’s disease (AD). Severe hyperhomocysteinemia causes neurological deficits and worsens behavioral and biochemical traits associated with AD. Although Hcy is precluded from entering the Genetic Code by proofreading mechanismsofaminoacyl-tRNAsynthetases, andthusisanon-proteinaminoacid,itcan be attached to proteins via an N-homocysteinylation reaction mediated by Hcy-thiolactone. Because N-homocysteinylation is detrimental to a protein’s function and biological integrity, Hcy-thiolactone detoxifying enzymes—PON1, BLMH, BPHL—have evolved. This narrative review provides an account of the biological function of these enzymes and of the consequences of their impairments, leading to the phenotype characteristic of AD. Overall, accumulating evidence discussed in this review supports a hypothesis that Hcy-thiolactone contributes to neurodegeneration associated with a dysregulated Hcy metabolism.
dc.affiliationWydział Rolnictwa, Ogrodnictwa i Biotechnologii
dc.affiliation.instituteKatedra Biochemii i Biotechnologii
dc.contributor.authorJakubowski, Hieronim
dc.date.access2025-04-09
dc.date.accessioned2025-06-26T06:26:21Z
dc.date.available2025-06-26T06:26:21Z
dc.date.copyright2024-07-25
dc.date.issued2024
dc.description.abstract<jats:p>Elevated levels of homocysteine (Hcy) and related metabolites are associated with Alzheimer’s disease (AD). Severe hyperhomocysteinemia causes neurological deficits and worsens behavioral and biochemical traits associated with AD. Although Hcy is precluded from entering the Genetic Code by proofreading mechanisms of aminoacyl-tRNA synthetases, and thus is a non-protein amino acid, it can be attached to proteins via an N-homocysteinylation reaction mediated by Hcy-thiolactone. Because N-homocysteinylation is detrimental to a protein’s function and biological integrity, Hcy-thiolactone-detoxifying enzymes—PON1, BLMH, BPHL—have evolved. This narrative review provides an account of the biological function of these enzymes and of the consequences of their impairments, leading to the phenotype characteristic of AD. Overall, accumulating evidence discussed in this review supports a hypothesis that Hcy-thiolactone contributes to neurodegeneration associated with a dysregulated Hcy metabolism.</jats:p>
dc.description.accesstimeat_publication
dc.description.additionalSpecial Issue Homocysteine in Protein Structure and Function and Human Disease
dc.description.bibliographyil., bibliogr.
dc.description.financepublication_nocost
dc.description.financecost0,00
dc.description.if4,9
dc.description.number15
dc.description.points140
dc.description.versionfinal_published
dc.description.volume25
dc.identifier.doi10.3390/ijms25158095
dc.identifier.eissn1422-0067
dc.identifier.issn1661-6596
dc.identifier.urihttps://sciencerep.up.poznan.pl/handle/item/2886
dc.identifier.weblinkhttps://www.mdpi.com/1422-0067/25/15/8095
dc.languageen
dc.relation.ispartofInternational Journal of Molecular Sciences
dc.relation.pagesart. 8095
dc.rightsCC-BY
dc.sciencecloudnosend
dc.share.typeOPEN_JOURNAL
dc.subject.enBLMH
dc.subject.enBPHL
dc.subject.enPON1
dc.subject.enhomocysteine thiolactone
dc.subject.enPHF8
dc.subject.enmTOR signaling
dc.subject.enautophagy
dc.subject.enAlzheimer’s disease
dc.subtypeReviewArticle
dc.titleHomocysteine Thiolactone Detoxifying Enzymes and Alzheimer’s Disease
dc.typeJournalArticle
dspace.entity.typePublication
oaire.citation.issue15
oaire.citation.volume25