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Relation Between Alzheimer' Disease And ERK Pathway With PKC And GDNF

Posted on:2003-01-21Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z WuFull Text:PDF
GTID:1104360092995851Subject:Cell biology
Abstract/Summary:PDF Full Text Request
ObjectiveWith the prolong of human expectative life, aging of the population and dementia are increasing. The elderly dementia is not only individual disease, but also giving great burden to the society, and becomes an important society commonality problem. AD is an important kind of elderly dementia, AD is a primary degenerative elderly dementia, it's characteristic is attacking at early age, most before 65 years old, so is called early elderly dementia, it's progress is slow, and main manifestations are deceasing in memory, and in neurochemistry, often deficits in many neurotransmitters. It is studied early and thorouly in developing country. Our country have made some results in studying AD.Early manifestations of AD are mainly memory defects in the hippocampi lesions , then the cerebral cortex lesions, it leads to not only deterioration of memory, but also defects in other cognitive abilities for example, the language,space structure abilities. About pathological mechanisms of AD, at present definitive ones are: (1) Acetylcholinergic( Ach) neurons degeneration and loss in basal forebrain neuclei; (2) Neurofibrillary tangles formed in patients brain; (3) A-mounts of myloid deposits appear in neocortex and hippocampi , the amounts are positive correlating to severities of AD. Establishing a reliable AD animal model is the precondition, there are many AD animal models, they all have virtues anddefects, there isn't a recognized perfect method until now. Here we select intra-hippocampal septal grafts in rats with fimbria - fornix lesions to construct AD model, this method mainly grafts in septal - hippocampi route, destroying ace-tylcholinergic and nonacetylcholinergic fibers afferent, leading experimental animals defects in the movements and neurochemistry, made animals abnormal in space directional and memory, and loss of acetylcholinergic neurons.Ubiquitin is a single 8,565 Da polypeptide chain of 76 amino acids. This small protein which has remained highly conserved throughout the evolution is u-niversally present in all living cells. Ubiquitin is belived to play a regulatory role in eukaryotic cells by forming conjugates with acceptor protein via a peptide or isopepotide bond between its carboxy terminal residue, glycine and primary a ?or e - amino groups of that of the target proteins. This ubiquitination of proteins is believed to serve as a signal for their intracellular degradation by adenosine 5' - triphosphate( ATP) - dependent proteolysis. Furthermore, ubiquitin itself has been reported to have proteaeae activity in vitro.Protein kinase C is a kind of kinase that distributes widely in eukaryotie, especially in mammals cells, is a family that consisted of many kinds of isoenzymes, they have similar structures, but different biochemical characteristics and physiological function. Through molecular clone techniques, it proves that PKC is not single molecular enzyme, and that the family with a group of correlated closely many kinds of subtypes. PKC have many subtypes , and every one displays different enzymatic characteristics and tissue expression, and special location in cell. Now, there are 12 kinds of subtypes definitely in animal tissue, and they have been grouped and named.GDNF has been identified as a potent neurotrophic factor that enhances survival of midbrain dopaminergic neutons. GDNF is a glycosylated, disulfide -bonded homodimer and is a distantly related member of the TGF jisuperfamily of growth regulatory ligands. GDNF contains the seven conserved cysteine residues in the same relative spacing characteristic of all members of the TGF psuperfamily. In embryonic midbrain cultures, GDNF promotes the survival and morphological differentiation of dopaminergic neurons and increase their high-affinity sopamine uptake. On the basis of these findings, it has been suggested that GDNF may have utility in the treatment of Parkinson's disease, which is marked by progressive degeneration of midbrain dopaminergic neurons.MAPKs is a family of serine/threonine ( Ser/Thr)...
Keywords/Search Tags:Alzheimer's disease, ubiquitin protein kinase C, Glial cell line - derives neurotrophic factor, extracellular regulated protein kinase, intrahippocampal septal grafts in rats with fimbria - fornix lesions
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