[Alzheimer's disease: new prospects in therapy and applied experimental models].
Neurodegenerative disorders such as Alzheimer's disease (AD) are the most common disease of modern society. The gradual and irreversible disturbances in homeostasis are characteristic features of the disease process. The cardinal features of AD include the formation of extracellular protein deposits in the brain that consist predominantly of aggregates of b amyloid protein(senile plaques), neurofibrilary tangles (hyperfosforylated tau protein) in the intracellular compartments,disturbances in calcium homeostasis, and degeneration/loss of synapses and neurons. An inflammatory process in the central nervous system is believed to play an important role in the pathway leading to neuronal cell death. The inflammatory response is mediated by activated microglia, resident immune cells of the central nervous system. Chronic activation of the microglia and astrocytes may cause damage of the brain-blood barrier and neuronal damage through the release of potentially cytotoxic molecules such as proinflammatory cytokines, reactive oxygen species, NO, and complement proteins. These alterations cause influx of immunocompetent cells from the periphery and their active participation in the local inflammatory reaction. Disturbances in the control mechanism of the inflammatory processes leads to perturbations in function and extensive brain degeneration. A characteristic symptom of AD dementia, is associated with dysfunctions of cognitive memory such as calculation, space orientation, and speech impairment. By tracking the sequence of events leading to the Alzheimer's type of dementia, the therapeutic possibilities can be combined with modulation of secretase activation responsible for the formation of amyloidogenic forms Abeta(40-43), inhibition of aggregation or beta amyloid deaggregation,and regulation of the inflammatory response. Several strategies for drug intervention in both the treatment and prevention of AD has been pursued, but so far there is no fully effective cure without side effects. Transplantation of nerve cells and genetic therapy are looked upon as new perspectives. Research is being conducted on the application of proteins deforming beta-sheet structures. Due to the pluricausal and multidirectional type of biological changes characteristic of AD, it seems likely that multidrug therapy or multidirectional medicine would be more efficient. Post-mortem experiments as well as neurochemical and anatomical brain studies helps to reveal new facts about the mechanisms underlying brain diseases. However limited access to fresh brain tissues or primary cell lines, which would be the best experimental models, compel researchers to look for other experimental models allowing investigation of disease occurrence. It seems that transgenic animals fulfill the requirements of relecting the disease process. In spite of the wide range of applied experimental models it is difficult to fi nd clear answers to such questions as what are the exact stages of neurodegenerative process? How and what kind of factor could stop, slow down, or prevent this alterations? These questions are still open.
Kubis
Adriana M
AM
Zakład Biotechnologii Białek, Wydział Biotechnologii, Uniwersytet Wrocławski, ul. Tamka 2, 50-137 Wrocław. adriana_kubis@yahoo.com
Janusz
Maria
M
D000544:Alzheimer Disease / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D014015:Tissue Banks; D016875:tau Proteins / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D016207:Cytokines; D017382:Reactive Oxygen Species; D016875:tau Proteins