Amyloid β perturbs elevated heme flux induced with neuronal development

Chantal Vidal, Kelly Daescu, Keely E. Fitzgerald, Anna Starokadomska, Ilya Bezprozvanny, Li Zhang

Research output: Contribution to journalArticle

Abstract

Introduction: Heme is a central molecule in mitochondrial respiration and ATP generation in neuronal cells. Thus, we assessed the importance of altered heme metabolism in Alzheimer's disease (AD) pathogenesis. Methods: To investigate the role of altered heme metabolism in AD, we identified heme-related proteins whose expression is altered in AD patients and mouse models exhibiting amyloid pathology. We detected the levels of proteins involved in heme synthesis, uptake, degradation, and function during neuronal differentiation and characterized the effects of Aβ. Results: We found that the expression levels of the rate-limiting heme synthetic enzyme ALAS1 and heme degradation enzyme HO-2 are selectively decreased in AD patients and mice. Aβ selectively reduces the levels of HO-2 and heme degradation, which are elevated to support neuronal functions in fully differentiated neuronal cells. Discussion: Our data show that lowered heme metabolism, particularly the decreased levels of heme degradation and HO-2, is likely a very early event in AD pathogenesis.

Original languageEnglish (US)
Pages (from-to)27-37
Number of pages11
JournalAlzheimer's and Dementia: Translational Research and Clinical Interventions
Volume5
DOIs
StatePublished - 2019

Keywords

  • Alzheimer's disease
  • Amyloid β
  • Heme
  • Heme degradation
  • Heme oxygenase

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health

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