Construction and identification of amyloid beta (A4) precursor protein
Construction and identification of amyloid beta (A4) precursor protein cleaving enzyme specific small interfering RNA eukaryotic expression vector
Alzheimer's disease (Alzheimers disease AD), is a serious disease of the central nervous system, one of the patients due to death of nerve cells, memory skills, language ability and perceived competence is an overall decline, and ultimately death due to brain failure. Senile plaques (senile plaque, the SP) is one of the main pathological features of Alzheimer's disease. The starch cascade theory that the core component of the senile plaques of amyloid beta (A4) precursor protein ([Only registered users see links. ]) is the main reason of AD. APP is the amyloid precursor protein (amyloid of precursor protein, APP) by β-amyloid precursor protein cleaving enzyme (βsite APP cleaving by enzyme of BACE) and γ-secretase cleavage of. Are many ways to reduce APP generated, the most convenient and direct inhibition of BACE to reduce the generation of APP. Therefore, inhibition of BACE to be an important target for the design of therapeutic AD drugs, and widespread concern.
The study found that a large number of APP deposition around the nerve cells of Alzheimer's disease. APP deposition on neuronal toxic and plays an important role in the pathogenesis of AD. APP plays a vital role in the pathogenesis of AD, thus reducing APP production, speed up their removal, to prevent the aggregation of APP and the formation of toxic amyloid plaque against APP toxicity and suppression of their immune and inflammatory The reaction can become AD treatment strategies. So whether it is direct or indirect method of treatment, all targeting of APP. AD therapy, many scholars are optimistic about the role in the secretion of enzymes from the root because it can reduce the generation of APP from the source to prevent the progression of AD. To reduce the production of APP in theory in three ways: ① α-secretase agonist, APP to avoid beta pathway, reducing the generation of APP; ② of BACE inhibitor; ③ gamma-secretase inhibitors. BACE inhibitor is more and more attention. In order to confirm the inhibition of BACE does not produce toxic effects on normal tissues and cells, several research groups BACE knockout experiments.That these gene deficient mice (of BACE-/ -) grew normally analysis results with normal mice (of BACE + / +) no significant difference in morphology, hematology, and animal behavior, but of BACE - / - mice brain and cultured neurons BACE activity disappeared.The use of BACE - / - mice and Swedish APP over-expression in transgenic mice mating of the second generation of mice in excess of APP. Embryonic neural cells using expression of APP adenovirus infection in the absence of BACE, the display does not produce mass spectrometry and gel electrophoresis analysis of APP. In vitro analysis also found that in of BACE - / - mouse brain and cultured neural cell extract undetectable APP and BACE activity. These experiments confirmed that BACE is the major β-secretase enzyme in the body, inhibition of BACE activity in the body do not cause high toxicity. The minds of the BACE-deficient mice do not produce APP, confirmed through the inhibition of BACE activity to reduce the level of APP in order to achieve the purpose of treatment or mitigation of AD symptoms, and provide an experimental basis for the feasibility of BACE as a therapeutic target in AD.