Analysis of the genes coding for subunit 10 and 15 of cytochrome c oxidase in Alzheimer's disease

Massimiliano Vitali, Eliana Venturelli, Daniela Galimberti, Luisa Benerini Gatta, Elio Scarpini, Dario Finazzi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Decay of mitochondria and oxidative stress are associated with normal aging, but many neurodegenerative diseases, and particularly Alzheimer's disease (AD), are characterized by a significant increase in the intensity of these traits. Recent data suggest the possible contribution of heme deficiency to the progressive derangement of mitochondria in AD brain; shortage of heme, and particularly of heme-a, actually leads to loss of mitochondrial cytochrome c oxidase (COX), abnormal production of reactive oxygen species and altered amyloid precursor protein metabolism. We reasoned that differences in the amount and/or functioning of COX assembly subunit 10 (COX10) and 15 (COX15), the key enzymes involved in heme-a biosynthesis, could be linked to variations of the individual risk to develop AD. We analyzed their mRNA expression in the hippocampus from AD patients and controls, investigated the existence of nucleotide variations in their DNA sequences and analyzed their distribution in large groups of AD and control individuals. COX 15 mRNA was significantly more abundant in the cerebral tissue of AD patients (3.18 ± 1.70 vs. 1.22 ± 0.66 μg, normalized dose, P = 0.01). The IVS-178G>A SNP in COX10 and the c+1120C>T SNP in COX15 were significantly less represented in the patient group (P <0.001 and P = 0.017, respectively) with respective odd ratios of 0.22 and 0.59, suggesting a possible protective role toward the risk for AD.

Original languageEnglish
Pages (from-to)1635-1641
Number of pages7
JournalJournal of Neural Transmission
Volume116
Issue number12
DOIs
Publication statusPublished - Jan 2009

Fingerprint

Electron Transport Complex IV
Alzheimer Disease
Genes
Heme
Single Nucleotide Polymorphism
Mitochondria
Oxidoreductases
Messenger RNA
Amyloid beta-Protein Precursor
Neurodegenerative Diseases
Reactive Oxygen Species
Hippocampus
Oxidative Stress
Nucleotides
Odds Ratio
Brain
Enzymes

Keywords

  • Alzheimer's disease
  • COX10
  • COX15
  • Cytochrome c oxidase
  • Heme
  • SNP

ASJC Scopus subject areas

  • Biological Psychiatry
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Analysis of the genes coding for subunit 10 and 15 of cytochrome c oxidase in Alzheimer's disease. / Vitali, Massimiliano; Venturelli, Eliana; Galimberti, Daniela; Benerini Gatta, Luisa; Scarpini, Elio; Finazzi, Dario.

In: Journal of Neural Transmission, Vol. 116, No. 12, 01.2009, p. 1635-1641.

Research output: Contribution to journalArticle

Vitali, Massimiliano ; Venturelli, Eliana ; Galimberti, Daniela ; Benerini Gatta, Luisa ; Scarpini, Elio ; Finazzi, Dario. / Analysis of the genes coding for subunit 10 and 15 of cytochrome c oxidase in Alzheimer's disease. In: Journal of Neural Transmission. 2009 ; Vol. 116, No. 12. pp. 1635-1641.
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