)| PMID |
9762518 ( ) |
|---|---|
| Title | The importance of inflammatory mechanisms in Alzheimer disease. |
| Abstract | Lesions in such chronic neurodegenerative disorders as Alzheimer disease (AD), Parkinson disease, the parkinsonism dementia complex of Guam, and amyotrophic lateral sclerosis have associated with them a variety of proteins known to be involved in inflammatory processes. This is particularly true of AD, where inflammatory reactions are thought to be important contributors to the neuronal loss. Proteins present include complement proteins, complement inhibitors, acute phase reactants, inflammatory cytokines, proteases, and protease inhibitors. Studies of cultured human astrocytes and microglia, obtained from postmortem brain, have established that nearly all of these proteins are produced by one or another of these cell types. Human neurons also produce many inflammatory proteins and their inhibitors, creating complex interactions. Accumulations of amyloid and extracellular tangles apparently act as irritants, causing the activation of complement, the initiation of reactive changes in microglia, and the release of potentially neurotoxic products. Such products include the membrane attack complex, oxygen free radicals, and excess glutamate. Twenty epidemiological studies that have been published to date indicate that populations taking antiinflammatory drugs have a significantly reduced prevalence of AD or a slower mental decline. One small clinical trial with indomethacin showed arrest of the disease over a six-month period. Therapeutic intervention in key inflammatory processes holds great promise for the amelioration of AD and possibly other neurodegenerative disorders. Columbia, Vancouver, Canada. mcgeerpl@unixg.ubc.ca |
NOTE: Color highlight is limited to the abstract and SciMiner text-mining mode. If you see much more identified targets below from "Targets by SciMiner Summary" and "Targets by SciMiner Full list", they may have been identified from the full text.
Targets by SciMiner Summary
| HUGO ID | Symbol | Target Name | #Occur | ActualStr |
|---|---|---|---|---|
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | 6 | amyloid | |
| 1323 | C4A | complement component 4A (Rodgers blood group) | 5 | C4a | C4b | |
| 1338 | C5AR1 | complement component 5a receptor 1 | 2 | C5a | |
| 2367 | CRP | C-reactive protein, pentraxin-related | 1 | c reactive protein | |
| 1929 | CHGA | chromogranin A (parathyroid secretory protein 1) | 1 | chromogranin a | |
| 21210 | LPAL2 | lipoprotein, Lp(a)-like 2 | 1 | apolipoprotein | |
| 3530 | F12 | coagulation factor XII (Hageman factor) | 1 | hageman factor | |
Targets by SciMiner Full list
| HUGO ID | Symbol | Name | ActualStr | Score | FlankingText |
|---|---|---|---|---|---|
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 2.3 | Accumulations of amyloid and extracellular tangles apparently act as irritants causing the activation |
| 1323 | C4A | complement component 4A (Rodgers blood group) | C4a | 1.1 | cleaves multiple molecules of both C4 and C2 to generate C4a C4b C2a and C2b |
| 1323 | C4A | complement component 4A (Rodgers blood group) | C4b | 1.1 | multiple molecules of both C4 and C2 to generate C4a C4b C2a and C2b |
| 1323 | C4A | complement component 4A (Rodgers blood group) | C4b | 1.1 | The C4b and C2a fragments combine to form the C3 convertase which |
| 1323 | C4A | complement component 4A (Rodgers blood group) | C4b | 1.1 | Both C3b and C4b have thiol groups exposed that can form covalent bonds with |
| 1338 | C5AR1 | complement component 5a receptor 1 | C5a | 0.3 | C3 convertase yields the C5 convertase which cleaves C5 into C5a and C5b the latter combining with C6 C7 C8 and |
| 1323 | C4A | complement component 4A (Rodgers blood group) | C4a | 1.1 | The small diffusible fragments C4a C3a and C5a produced by complement activation are called anaphylatoxins |
| 1338 | C5AR1 | complement component 5a receptor 1 | C5a | 0.3 | The small diffusible fragments C4a C3a and C5a produced by complement activation are called anaphylatoxins because of their |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 2.3 | chromogranin A ( Taupenot et al . 1996 and _amp_#x3b2 -amyloid protein ( Klegeris et al . 1994 as well as |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 2.3 | activators of complement have for example been found in AD amyloid deposits |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 2.3 | The most prominent is _amp_#x3b2 -amyloid protein |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 2.3 | Others are amyloid P C-reactive protein and the Hageman factor ( McGeer and |
| 620 | APP | amyloid beta (A4) precursor protein (peptidase nexin-II, Alzheimer disease) | amyloid | 2.3 | Subsequent immunohistochemical and other studies have revealed that the amyloid deposits in AD are also associated with many other extracellular |
| 1929 | CHGA | chromogranin A (parathyroid secretory protein 1) | chromogranin a | 1.0 | activated microglia have been shown to be toxic to neurons in culture and some materials found in ad lesions namely chromogranin a taupenot et al . 1996 and _amp_#x3b2; amyloid protein klegeris et al . 1994 as well as complement proteins have been found to activate microglia in vitro. |
| 3530 | F12 | coagulation factor XII (Hageman factor) | hageman factor | 1.0 | others are amyloid p c reactive protein and the hageman factor mcgeer and mcgeer 1995 . |
| 2367 | CRP | C-reactive protein, pentraxin-related | c reactive protein | 1.0 | others are amyloid p c reactive protein and the hageman factor mcgeer and mcgeer 1995 . |
| 21210 | LPAL2 | lipoprotein, Lp(a)-like 2 | apolipoprotein | 1.0 | they used twins and individuals genotyped for apolipoprotein e4 an established risk factor for ad roses 1996 . |