Decreased brain protein levels of cytochrome oxidase subunits in Alzheimer's disease and in hereditary spinocerebellar ataxia disorders: a nonspecific change? - PubMed (original) (raw)

Comparative Study

Decreased brain protein levels of cytochrome oxidase subunits in Alzheimer's disease and in hereditary spinocerebellar ataxia disorders: a nonspecific change?

S J Kish et al. J Neurochem. 1999 Feb.

Abstract

Controversy exists as to the clinical importance, cause, and disease specificity of the cytochrome oxidase (CO) activity reduction observed in some patients with Alzheimer's disease (AD). Although it is assumed that the enzyme is present in normal amount in AD, no direct measurements of specific CO protein subunits have been conducted. We measured protein levels of CO subunits encoded by mitochondrial (COX I, COX II) and nuclear (COX IV, COX VIc) DNA in autopsied brain of patients with AD whom we previously reported had decreased cerebral cortical CO activity. To assess disease specificity, groups of patients with spinocerebellar ataxia type I and Friedreich's ataxia were also included. As compared with the controls, mean protein concentrations of all four CO subunits were significantly decreased (-19 to -47%) in temporal and parietal cortices in the AD group but were not significantly reduced (-12 to -17%) in occipital cortex. The magnitude of the reduction in protein levels of the CO subunits encoded by mitochondrial DNA (-42 to -47%) generally exceeded that encoded by nuclear DNA (-19 to -43%). In the spinocerebellar ataxia disorders, COX I and COX II levels were significantly decreased in cerebellar cortex (-22 to -32%) but were normal or close to normal in cerebral cortex, an area relatively unaffected by neurodegeneration. We conclude that protein levels of mitochondrial- and nuclear-encoded CO subunits are moderately reduced in degenerating but not in relatively spared brain areas in AD and that the decrease is not specific to this disorder. The simplest explanation for our findings is that CO is decreased in human brain disorders as a secondary event in brain areas having reduced neuronal activity or neuronal/synaptic elements consequent to the primary neurodegenerative process.

PubMed Disclaimer

Cited by

Amyloid precursor protein drives down-regulation of mitochondrial oxidative phosphorylation independent of amyloid beta.
Lopez Sanchez MIG, Waugh HS, Tsatsanis A, Wong BX, Crowston JG, Duce JA, Trounce IA. Lopez Sanchez MIG, et al. Sci Rep. 2017 Aug 29;7(1):9835. doi: 10.1038/s41598-017-10233-0. Sci Rep. 2017. PMID: 28852095 Free PMC article.
The Alzheimer's disease mitochondrial cascade hypothesis: an update.
Swerdlow RH, Khan SM. Swerdlow RH, et al. Exp Neurol. 2009 Aug;218(2):308-15. doi: 10.1016/j.expneurol.2009.01.011. Epub 2009 Jan 29. Exp Neurol. 2009. PMID: 19416677 Free PMC article. Review.
Energy hypometabolism in posterior cingulate cortex of Alzheimer's patients: superficial laminar cytochrome oxidase associated with disease duration.
Valla J, Berndt JD, Gonzalez-Lima F. Valla J, et al. J Neurosci. 2001 Jul 1;21(13):4923-30. doi: 10.1523/JNEUROSCI.21-13-04923.2001. J Neurosci. 2001. PMID: 11425920 Free PMC article.
Mitochondria-sequestered Aβ renders synaptic mitochondria vulnerable in the elderly with a risk of Alzheimer disease.
Jia K, Tian J, Wang T, Guo L, Xuan Z, Swerdlow RH, Du H. Jia K, et al. JCI Insight. 2023 Nov 22;8(22):e174290. doi: 10.1172/jci.insight.174290. JCI Insight. 2023. PMID: 37991017 Free PMC article.
Prospects for redox-based therapy in neurodegenerative diseases.
Friedlich AL, Beal MF. Friedlich AL, et al. Neurotox Res. 2000;2(2-3):229-37. doi: 10.1007/BF03033796. Neurotox Res. 2000. PMID: 16787843

Decreased brain protein levels of cytochrome oxidase subunits in Alzheimer's disease and in hereditary spinocerebellar ataxia disorders: a nonspecific change? - PubMed (original) (raw)