Brain β-amyloid accumulation in transgenic mice expressing mutant superoxide dismutase 1

Bradley J. Turner, Qiao Xin Li, Katrina M. Laughton, Colin L. Masters, Elizabeth C. Lopes, Julie D. Atkin, Surindar S. Cheema

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10 Citations (Scopus)

Abstract

Oxidative stress is implicated in both the deposition and pathogenesis of β-amyloid (Aβ) protein in Alzheimer's disease (AD). Accordingly, overexpression of the antioxidant enzyme superoxide dismutase 1 (SOD1) in neuronal cells and transgenic AD mice reduces Aβ toxicity and accumulation. In contrast, mutations in SOD1 associated with amyotrophic lateral sclerosis (ALS) confer enhanced pro-oxidative enzyme activities. We therefore examined whether ALS-linked mutant SOD1 overexpression in motor neuronal cells or transgenic ALS mice modulates Aβ toxicity or its accumulation in the brain. Aggregated, but not freshly solubilised, substrate-bound Aβ peptides induced degenerative morphology and cytotoxicity in motor neuron-like NSC-34 cells. Transfection of NSC-34 cells with human wild-type SOD1 attenuated Aβ-induced toxicity, however this neuroprotective effect was also observed for ALS-linked mutant SOD1. Analysis of the cerebral cortex, brainstem, cerebellum and olfactory bulb from transgenic SOD1 G93A mice using enzyme-linked immunosorbent assay of acid-guanidine extracts revealed age-dependent elevations in Aβ levels, although not significantly different from wild-type mouse brain. In addition, brain amyloid protein precursor (APP) levels remained unaltered as a consequence of mutant SOD1 expression. We therefore conclude that mutant SOD1 overexpression promotes neither Aβ toxicity nor brain accumulation in these ALS models.

Original languageEnglish
Pages (from-to)2281-2286
Number of pages6
JournalNeurochemical Research
Volume29
Issue number12
DOIs
Publication statusPublished - Dec 2004
Externally publishedYes

Keywords

  • Amyloid
  • amyloid protein precursor
  • amyotrophic lateral sclerosis
  • brain
  • NSC-34 cell
  • superoxide dismutase 1

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    Turner, B. J., Li, Q. X., Laughton, K. M., Masters, C. L., Lopes, E. C., Atkin, J. D., & Cheema, S. S. (2004). Brain β-amyloid accumulation in transgenic mice expressing mutant superoxide dismutase 1. Neurochemical Research, 29(12), 2281-2286. https://doi.org/10.1007/s11064-004-7037-z