NOX2 protein

by Séverine Altairac

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Our defense mechanism has no pity. Foreign matter for whom our organism can be a great playing field is rapidly dealt with. Virus, bacteria, pollen or even tumor cells face a merciless battle against the soldiers of our immune system: the white cells. Despite this, and however well-disposed these white cells may be, they cannot cross the cell barrier which isolates the brain from the rest of our body. So how does such a vital organ fight off invaders? The answer is: microglia.

Microglia are brain cells that carry a particularly offensive weapon: the NOX2 protein. This enzyme is lodged within the cells’ membrane and is involved in the synthesis of free radicals. Free radicals are particularly dangerous in that they can alter cell constituents and, as a result, are a menace to cell survival. Bacteria, for instance, are very sensitive to free radicals, making NOX2 a great candidate in the midst of bacterial infection. And how about neurons? Are they resistant to NOX2?

No… NOX2 is two-faced… Such was the recent discovery made by Karl-Heinz Krause and his team at the University of Geneva. Indeed, NOX2 seems to be involved in Alzheimer’s disease – a devastating infliction. Alzheimer’s is a pathology which affects a person’s cognitive and behavioral response, and entails the progressive death of neurons coupled with extracellular protein deposits: the amyloid plaques. The accumulation of such plaques does not go unnoticed and microglia – as they should – set off to demolish them. How? By producing free radicals thanks to NOX2. There is a major drawback though: neurons cannot cope with NOX2 invasion either and they are progressively destroyed. The good news is that such a discovery could be the basis for the development of a novel therapy. A decrease in NOX2 activity, for instance, could also decrease neuron death and hence the progression of the disease.

Alzheimer’s disease is the most common form of dementia in the western world, which afflicts – mainly - the elderly of 80 and over. And with populations ageing, it is fast becoming a public health issue…

Also read: "Alzheimer's disease : when the mind goes astray".

UniProt cross references
Cytochrome b-245 heavy chain (NOX2), Homo sapiens (human): P04839
Protein Spotlight (ISSN 1424-4721) is a monthly review written by the Swiss-Prot team of the SIB Swiss Institute of Bioinformatics. Spotlight articles describe a specific protein or family of proteins on an informal tone. Follow us: Subscribe · Twitter · Facebook