Expression And Significiance Of P38MAPK And JNK Pathways In Lymphocytes Of Alzheimer’s Disease And Parkinson’s Disease Patients

Alzheimer’s disease (AD), a kind of dementia which is closely related toage, is the most common form of neurodegenerative disease and dementia andoften occurs during senectitude and presenium. The classical clinicalmanifestation is progressive cognitive dysfunction and neuropsychiatricsymptoms and the damage of behaviors. Alzheimer’s disease is a progressivedementing disorder characterized by selective neuron loss in the limbic systemand association regions of the neocortex. The characteristic histopathologicalterations in AD are neuritic or senile plaques (SPs) composed largely ofamyloid β-peptides (Aβ) and neuronal aggregates of abnormallyphosphorylated cytoskeletal proteins [neurofibrillary tangles (NFTs)]. In ourcountry, there are a hundred and twenty million old people over60years, andthe morbidity of dementia is3-8%, Alzheimer’s disease accounting for morethan60%.Parkinson’s disease(also known as shaking palsy) got it’s name becauseit was described systematically by English doctor James Parkinson in1817. Itis the second most common neurodegenerative disease, the morality rank onlysecond to Alzheimer’s disease. There are approximate six millon Parkinson’sdisease patients all over the world. The people aged40-70can be patients,especially those whose ages range from50to60. In china, the morbidity ofpeople aged55-65is1%, and the incidence of Parkinson’s disease increaseswith increasing age and the males is more than females.With the rapid growth of the elderly population, the aging problem isdrawing more and more attention in the world, the incidence of Alzheimer’sdisease and Parkinson’s disease has been increasing in recent years. AD hasbecome the fourth disease which led to human death after tumor,cardiovascular disease and cranial vascular disease. Alzheimer’s disease and Parkinson’s disease seriously affect the quality of life in patients with them,and their self-care ability in late period of disease will have a heavy loss whichbrings about social and family financial burden and care burden greatly. Up tonow, although the underlying pathological mechanism led to Alzheimer’sdisease and Parkinson’s disease is not been fully defined, a large amount ofresearches demonstrate that the apoptosis of nerve cells occupies an importantposition in the pathogenesis of Alzheimer’s disease and Parkinson’s disease.Moreover, there are researches display that apoptosis occurs in the early stageof AD, not confined to nerve cells, but also embodied in peripheral bloodlymphocytes and fibroblasts. In the not too distant past, some studies alsodemonstrated that apoptosis consisted in Parkinson’s disease, in addition to thebrain neurons, it could also be founded in the peripheral blood lymphocytes.P38mitogen activated protein kinase(p38MAPK) and c-Jun N-terminalkinase(JNK) belong to mitogen activated protein kinases, and they are twoimportant members of MAPK family. They are serine/threonine proteinkinases and widely expressed in mammalian cells. P38MAPK and JNKsignaling pathways both can be activated by the ultraviolet rays、the alterationof the osmotic pressure、the variety of cell factors and physiological stress etc.,known collectively as mitogen activated protein kinase(MAPK) stress-activated signaling pathways. P38MAPK and JNK can play an important rolein mediating a large number of cellular reactions, such as inflammatoryreaction and stress, besides these, they are also closely related to cell growth、cell development and cell differentiation.More and more studies found that the alteration of expression and activityof P38MAPK and JNK can regulate and block the critical signaling pathwayseffectively and regulate cell apoptosis.The collection of peripheral blood is convenient, providing a simple anduseful model for researching the function of apoptosis events in Alzheimer’sdisease and Parkinson’s disease and looking for the target spot of intervention.If we can obtain convenient and effective land-marks, it will have a positiveimpact on the diagnosis and treatment of Alzheimer’s disease, but there is not yet such landmarks to this day.Objective: Firstly In this study, we researched the expression of stress-activated protein kinase P38MAPK and JNK in Alzheimer’s disease andParkinson’s disease patients’ peripheral blood lymphocytes at protein level,offering a cell model for screening diseases’ target spot of interve-tion.Secondly We studied the expression and activated levels of P38MAPKand JNK, the relative kinases which regulate apoptosis, looking for specificperipheral landmarks that are used for the diagnosis of AD.Thirdly At the same time, we detected the P38MAPK and JNKexpression levels in the normal people and Parkinson’s disease patientsrespectively, whose ages and the level of education matched with the ADpatients’, explicating the specificity of these indexes.Methods: Firstly We screened patients respectively on the basis of thediagnostic criteria of probable Alzheimer’s disease which was drew up bynational institute of neurological and communicative disorders and stroke andthe Alzheimer’s disease and related disorders association (NINCDS-ADRDA)and the diagnostic criteria about Parkinson’s disease that was formulated byChinese Medical Association in2006. We total collected20AD patients,20PD patients and20normal control people in the neurology clinic of the secondhospital affiliated to HeBei medical university hospital from2010.9to2011.12. After the consent of all subjects or their guardians, we gavecomprehensive assessment about them and recorded their personalinformation.Secondly All subjects underwent a15-mL venous blood samplingbetween9and11AM which then was placed in anti-coagulation tubes, afteran overnight fast; Peripheral blood lymphocytes were isolated by Ficolldensity gradient centrifugation.Thirdly Extract total protein from the peripheral lymphocytes anddetect the protein expression level of P38、P-P38、JNK and P-JNK throughWestern Blotting technology.Fourthly Statistic Analysis. Treat the statistics using SPSS17.0. Results: Both P-P38and P-JNK levels were augmented in PBLs of ADand PD patients in compared with controls (P＜0.05), however, the differentbetween AD and PD (P＞0.05) was no significant difference; Total P38andJNK levels both were no significant difference in AD and PD patients (P＞0.05) compared with controls.Conclusions：Firstly We confirmed the being and expression of stress-activated protein kinase P38MAPK and JNK in AD and PD patients’peripheral blood lymphocytes at protein level, which might offer a convenientand useful cell model for screening diseases’ target spot of interve-tion.Secondly Our results displayed the abnormal expression of P38MAPKand JNK signaling pathways not only existed in the central nervous system,but also could be detected in the peripheral lymphocytes in AD patients.Therefore, they might become the peripheral landmarks of AD diagnosis andevaluation of patients’ condition.Thirdly The abnormal expression of P38MAPK and JNK signalingpathways could also be detected in the peripheral lymphocytes in PD patients，which verified that was not owned by some a disease, but might exist in avariety of neurodegenerative disorders.