The origin and influence of Amyloid β-protein
The definition of Amyloid β-protein
Amyloid β-protein is a polypeptide of 39-43 amino acids which is produced by the proteolysis of Amyloid precursor protein (APP) via β-and γ-secretase. It can be produced by a variety of cells, circulating in the blood, cerebrospinal fluid and brain interstitial fluid, mostly with the chaperone protein molecules, a small number of free state exists. The most common subtypes of Amyloid β-protein in the human body are Amyloid β-protein 1-40 and Amyloid β-protein 1-42. In human cerebrospinal fluid and blood, Amyloid β-protein1 ~ 40, respectively, than Amyloid β-protein1 ~ 42 levels of 10 times higher and 1. 5 times, Amyloid β-protein1 ~ 42 with more toxic, and more easily gathered to form the core of Amyloid β-protein precipitation, triggering neurotoxicity.
1、Neurotoxicity of Amyloid β-protein In 1991, Kowall injected Amyloid β-protein into the cerebral cortex of rats and monkeys and found that tissue necrosis, peripheral neuron deletion and keratinocyte proliferation occurred at the injection site. Amyloid β-protein make vascular wall starch changes, a direct result of hardening of the arteries, elastic deterioration, or even easy to rupture or thrombosis, but also to induce premature apoptosis of nerve cells. Animal experiments show that Amyloid β-protein on the role of neurons and their state. Amyloid β-protein in a dissociative state promotes neurite outgrowth and neuron survival in a short period of time, whereas deposition of Amyloid β-protein has the opposite effect on neurons, leading to pathological changes similar to those of Alzheimer's disease, most notably occurs in the aging mammalian brain.
2、 Affect the shape and function of blood vessels Amyloid β-protein is first deposited on the extravascular basement membrane and then infiltrates into the smooth muscle cell layer. Amyloid β-protein deposition reduces the adhesion of small artery smooth muscle cells to the basement membrane, the middle layer of blood vessels is replaced by Amyloid β-protein, and the smooth muscle cells degeneration. Vinters, etc. and Yamaguchi study found that Amyloid β-protein deposition in the capillary basement membrane, and was a plate into the neural mat. Capillary Amyloid β-protein40 / Amyloid β-protein42 ratio was significantly lower than arteries. Therefore, Amyloid β-protein40 deposition mainly in the arterial wall, and Amyloid β-protein42 is deposited in the capillaries. Amyloid β-protein causes deposition of vascular fibers around the blood vessels, leading to Amyloid angiopathy.
3、Reduced the expression of fibroblast growth factor 2 Amyloid β-protein via the fibroblast growth factor 2 pathway on the vascular endothelial cells through the autocrine / paracrine pathway. Amyloid β-protein blocks the action of the FGF-2 axis by interacting with the cell membrane receptors of FGF-2. The point mutations of APP lead to the mutations of Amyloid β-protein21 ~ 23 amino acids. These mutants are closely related to the different genetic phenotypes of Amyloid angiopathy, the degree of cerebral vascular tropism, the reconstruction of damaged microvessels, and the proliferation of blood vessels.
Basic information on monoclonal antibodies
The discovery of monoclonal antibodies
In 1975 molecular biologists GJF Koehler and C. Milstein in the natural hybridization technology, based on the establishment of hybridoma technology, they can be cultured in vitro and mass proliferation of mouse myeloma cells and antigen-immunized pure Mouse splenic cell fusion, a hybrid cell lines, both with tumor cells in vitro easy to unlimited proliferation characteristics, but also with the antibody-forming cells synthesis and secretion of specific antibodies. This hybridoma can be cultured as a single cell, forming a single cell line, i.e., monoclonal. A large number of highly concentrated and very homogeneous antibodies can be obtained by culturing or intraperitoneally inoculating mice, and the structure, amino acid sequence, and specificity of the antibody are uniform, and in the course of culturing, as long as there is no variation, Time secreted by antibodies can maintain the same structure and function. This monoclonal antibody can not be obtained by other methods.
The use of monoclonal antibodies in life
Monoclonal antibodies can be used to explore the fine structure of the protein; the surface of the new subpopulations of lymphocyte subsets; histocompatibility antigens; hormone and drug radioimmunoassay (or enzyme immunoassay); tumor localization and classification; purification of microbial and parasitic antigens ;immunotherapy and drug-binding immuno-chemotherapy ( "missile" therapy, the use of monoclonal antibodies and target cells specific binding, bring the drug to the lesion).
Therefore, monoclonal antibodies can be directly used in the diagnosis of human disease, prevention, treatment and immune mechanisms of research for human malignancy immunodiagnosis and immunotherapy has opened up broad prospects
Advantages and Limitations
- The advantages of monoclonal antibodies
(1) Hybridomas can survive and pass "permanently" in vitro, and produce highly specific, highly homogeneous antibodies as long as they do not mutate into cell lines.
(2) a large number of highly specific, homogeneous antibodies can be obtained with relatively impure antigens.
(3) Since it is possible to obtain an "unlimited amount" of homogeneous antibodies, it is suitable for immunological analysis methods characterized by labeled antibodies, such as IRMA and ELISA.
(4) due to the high specificity of monoclonal antibodies and a single biological function, can be used for in vivo radioimmunoimaging and immunological therapy.
- The limitations of monoclonal antibodies
(1) the intrinsic affinity of the monoclonal antibody and the limitations of its biological activity limit its scope of application. Since monoclonal antibodies can not carry out precipitation and agglutination, many detection methods can not be completed with monoclonal antibodies.
(2) monoclonal antibody response than the intensity of polyclonal antibodies.
(3) preparation technology is complex, and time-consuming labor, so the price of monoclonal antibodies are higher.