Accumulation of neurotoxic amyloid- is a major hallmark of Alzheimer’s disease.

Question

Accumulation of neurotoxic amyloid- is a major hallmark of Alzheimer’s disease. Formation of amyloid- is catalyzed by [____], a protease with numerous substrates, some of which are required for normal development. Recently, a novel -secretase activating protein (GSAP) was discovered that drastically and selectively [____] amyloid- production through a mechanism involving its interactions with both -secretase and its substrate, the amyloid precursor protein. Recombinant GSAP stimulates amyloid- production in vitro. Reducing GSAP concentrations in cell lines [____] amyloid- concentrations. Gene ablation (knockdown) of GSAP in a mouse model of Alzheimer’s disease reduces levels of [____] and plaque development. Thus, GSAP can serve as an [____] therapeutic target without affecting other key functions of -secretase.

(1) -secretase; reduces; increases; -secretase; effective

(2) amylase; eliminates; reduces; amyloid-; amyloid--eliminating

(3) -secretase; decreases; increases; -secretase; unusual

(4) -secretase; inhibits; increases; -secretase; amyloid--directed

(5) -secretase; increases; decreases; amyloid-; amyloid--lowering

Explanation / Answer

(3) -secretase; decreases; increases; -secretase; unusual

Accumulation of neurotoxic amyloid- is a major hallmark of Alzheimer’s disease. Formation of amyloid- is catalyzed by [__-secretase__], a protease with numerous substrates, some of which are required for normal development. Recently, a novel -secretase activating protein (GSAP) was discovered that drastically and selectively [_decreases___] amyloid- production through a mechanism involving its interactions with both -secretase and its substrate, the amyloid precursor protein. Recombinant GSAP stimulates amyloid- production in vitro. Reducing GSAP concentrations in cell lines [_increases___] amyloid- concentrations. Gene ablation (knockdown) of GSAP in a mouse model of Alzheimer’s disease reduces levels of [_-secretase___] and plaque development. Thus, GSAP can serve as an [_unusual___] therapeutic target without affecting other key functions of -secretase.

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