Reduced homocysteine-thiolactonase activity in Alzheimer's disease

Joanna Suszynska, Joanna Tisonczyk, Hyoung Gon Lee, Mark A. Smith, Hieronim Jakubowski

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Elevated plasma homocysteine (Hcy) is a risk factor for Alzheimer's disease (AD). Bleomycin hydrolase (BLH), a thiol-dependent enzyme that has Hcy-thiolactonase (HTase) and aminopeptidease (APase) activities, has also been implicated in Alzheimer's disease (AD). In order to examine its role in AD, BLH activities were measured in postmortem brain tissue from twelve AD patients and twelve control patients who died from non-neurological causes. We found that HTase and APase activities in human brain extracts were strongly correlated and sensitive to the thiol reagent iodoacetamide, indicating that they are associated with BLH. Both activities were significantly decreased in brain tissue extracts from AD patients relative to controls (7.6 ± 4.2 vs. 13.5 ± 5.5 units, p= 0.003 for HTase, and 3.82 ± 1.27 vs. 5.33 ± 1.68 units, p=0.010 for APase). HTase and APase activities were positively correlated with N-linked protein Hcy, but not with tHcy, in AD and control brains. Levels of brain total Hcy and N-linked protein Hcy did not differ between AD cases and controls. These results suggest that diminished functional BLH activity could contribute to the pathology of AD.

Original languageEnglish (US)
Pages (from-to)1177-1183
Number of pages7
JournalJournal of Alzheimer's Disease
Volume19
Issue number4
DOIs
StatePublished - 2010

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Keywords

  • Alzheimer's disease
  • Aminopeptidase
  • Bleomycin hydrolase
  • Homocysteine- thiolactonase

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