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KMID : 1100220030020020120
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Dementia and Neurocognitive Disorders
2003 Volume.2 No. 2 p.120 ~ p.124
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Furin is an Important Regulator on Alpha-secretase Associated APP Processing
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Hwang Eun-Mi
Sim Hea-Jin
Mook-In-Hee
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Abstract
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Background: The β-amyloid protein, Aβ, which accumulates in the brains of Alzheimer’s disease patients, is derived by proteolysis of the amyloid precursor protein (APP). APP can undergo endoproteolytic processing at three sites, one at the amino terminus of the Aβ domain(by β-secretase), one within the Aβ domain (by α-secretase), and one at the carboxyl terminus of the Aβ domain (by γ-secretase). Constitutive and PKC-regulated α-secretase pathways have been reported to secrete sAPPα. In both pathways, we examined mechanisms of furin, which is known to regulate α-secretase activity.
Methods: Two methods were used to inhibit the activity of furin: overexpression of prodomain of furin and the infection of furin-specific inhibitor α-1-PDX adenovirus in a COS-7 cell. Real-Time PCR was used to determine the level of mRNA of furin in both the APP transgenic mice and age-matched control mice.
Results: As a result of inhibiting the activity of furin, the level of sAPPα was significantly decreased regardless of the PKC activity, and the total level of APP did not change as well. In a real-time PCR, there was a significant decrease in the mRNA of furin in APP transgenic mice compared to that of control.
Conclusion: Our results suggest that furin plays an important role in the processing of APP through α-secretase and that the decrease in the level of furin may be closely related to the mechanisms that lead to Alzheimer’s disease.
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KEYWORD
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Alzheimer’s disease, Furin, Alpha-secretase, Tg2576
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