Cyclooxygenases and 5-Lipoxygenase in Alzheimer's disease.
Summary of "Cyclooxygenases and 5-Lipoxygenase in Alzheimer's disease."
Typically, cyclooxygenases (COXs) and 5-lipoxygenase (5-LOX), enzymes that generate biologically active lipid molecules termed eicosanoids, are considered inflammatory. Hence, their putative role in Alzheimer's disease (AD) has been explored in the framework of possible inflammatory mechanisms of AD pathobiology. More recent data indicate that these enzymes and the biologically active lipid molecules they generate could influence the functioning of the central nervous system and the pathobiology of neurodegenerative disorders such as AD via mechanisms different from classical inflammation. These mechanisms include the cell-specific localization of COXs and 5-LOX in the brain, the type of lipid molecules generated by the activity of these enzymes, the type and the localization of receptors selective for a type of lipid molecule, and the putative interactions of the COXs and 5-LOX pathways with intracellular components relevant for AD such as the gamma-secretase complex. Considering the importance of these multiple and not necessarily inflammatory mechanisms may help us delineate the exact nature of the involvement of the brain COXs and 5-LOX in AD and would reinvigorate the search for novel targets for AD therapy.
Affiliation
Journal Details
This article was published in the following journal.
Name: Progress in neuro-psychopharmacology & biological psychiatry
ISSN: 1878-4216
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20691748
- DOI: http://dx.doi.org/10.1016/j.pnpbp.2010.07.032
Medical and Biotech [MESH] Definitions
Lipoxygenase
An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the ARACHIDONATE LIPOXYGENASES; ARACHIDONATE 5-LIPOXYGENASE; ARACHIDONATE 12-LIPOXYGENASE; and ARACHIDONATE 15-LIPOXYGENASE. EC 1.13.11.12.
Neuropil Threads
Abnormal structures located chiefly in distal dendrites and, along with NEUROFIBRILLARY TANGLES and SENILE PLAQUES, constitute the three morphological hallmarks of ALZHEIMER DISEASE. Neuropil threads are made up of straight and paired helical filaments which consist of abnormally phosphorylated microtubule-associated tau proteins. It has been suggested that the threads have a major role in the cognitive impairment seen in Alzheimer disease.
Alzheimer Vaccines
Vaccines or candidate vaccines used to prevent or treat ALZHEIMER DISEASE.
Aphasia, Primary Progressive
A progressive form of dementia characterized by the global loss of language abilities and initial preservation of other cognitive functions. Fluent and nonfluent subtypes have been described. Eventually a pattern of global cognitive dysfunction, similar to ALZHEIMER DISEASE, emerges. Pathologically, there are no Alzheimer or PICK DISEASE like changes, however, spongiform changes of cortical layers II and III are present in the TEMPORAL LOBE and FRONTAL LOBE. (From Brain 1998 Jan;121(Pt 1):115-26)
5-lipoxygenase-activating Protein Inhibitors
Compounds that bind to and inhibit the action of 5-LIPOXYGENASE-ACTIVATING PROTEINS.
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