Kim Taehyun, Hinton David J, Choi Doo-Sup
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Int J Alzheimers Dis. 2011 Jan 17;2011:857368. doi: 10.4061/2011/857368.
Alzheimer's disease (AD) is the most common form of dementia among the elderly population. AD, which is characterized as a disease of cognitive deficits, is mainly associated with an increase of amyloid β-peptide (Aβ) in the brain. A growing body of recent studies suggests that protein kinase C (PKC) promotes the production of the secretory form of amyloid precursor protein (sAPPα) via the activation of α-secretase activity, which reduces the accumulation of pathogenic Aβ levels in the brain. Moreover, activation of PKCα and mitogen-activated protein kinase (MAPK) is known to increase sAPPα. A novel type of PKC, PKCε, activates the Aβ degrading activity of endothelin converting enzyme type 1 (ECE-1), which might be mediated via the MAPK pathway as well. Furthermore, dysregulation of PKC-MAPK signaling is known to increase Aβ levels in the brain, which results in AD phenotypes. Here, we discuss roles of PKC in Aβ production and clearance and its implication in AD.
阿尔茨海默病（AD）是老年人群中最常见的痴呆形式。AD以认知缺陷疾病为特征，主要与大脑中淀粉样β肽（Aβ）的增加有关。最近越来越多的研究表明，蛋白激酶C（PKC）通过激活α-分泌酶活性促进淀粉样前体蛋白分泌形式（sAPPα）的产生，这减少了大脑中致病性Aβ水平的积累。此外，已知PKCα和丝裂原活化蛋白激酶（MAPK）的激活会增加sAPPα。一种新型的PKC，即PKCε，可激活1型内皮素转化酶（ECE-1）的Aβ降解活性，这也可能通过MAPK途径介导。此外，已知PKC-MAPK信号失调会增加大脑中的Aβ水平，从而导致AD表型。在此，我们讨论PKC在Aβ产生和清除中的作用及其在AD中的意义。
