Work

Overexpression of SOD-2 reduces hippocampal superoxide and prevents memory deficits in a mouse model of Alzheimer's disease

Year: 2009

Type: article

Abstract: Alzheimer's disease (AD) is a neurodegenerative disease characterized by impaired cognitive function and the deposition of extracellular amyloid plaques and intracellular tangles. Although the proximal cause of AD is not well understood, it is clear that amyloid-beta (Abeta) plays a critical role in AD pathology. Recent studies also implicate mitochondrial abnormalities in AD. We investigated this idea by crossing mice that overexpress mitochondrial superoxide dismutase (SOD-2) with the Tg2576 mouse model of AD that overexpresses the human amyloid precursor protein carrying the Swedish mutation (K670N:M671L). We found that overexpression of SOD-2 decreased hippocampal superoxide, prevented AD-related learning and memory deficits, and reduced Abeta plaques. Interestingly, SOD-2 overexpression did not affect the absolute levels of Abeta(1-40) and Abeta(1-42), but did significantly reduce the Abeta(1-42) to Abeta(1-40) ratio, thereby shifting the balance toward a less amyloidogenic Abeta composition. These findings directly link mitochondrial superoxide to AD pathology and demonstrate the beneficial effects of a mitochondrial anti-oxidant enzyme, hence offering significant therapeutic implications for AD.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.0902714106

Authors: Cynthia A. Massaad, Taneasha M. Washington, Robia G. Pautler, Eric Klann

Institutions: Baylor College of Medicine, New York University

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green