Presenilins--in search of functionality.
The discovery of the PS proteins, the complexities of their biochemistry and their potential involvement in signalling pathways and in apoptosis have galvanized research into AD. To date, the aspect of the functionality of the PSs most relevant to the pathology of AD is the effect of PS FAD mutants to increase the proportion of A beta 42 produced from cells. This, coupled to the observation that gamma-secretase cleavage is considerably reduced in neurons derived from PS-1 knockout mice, argues strongly that PS plays a very direct role in the proteolytic processing of APP.
Neurosciences Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, Essex, UK.
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Karran
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Allsop
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Christie
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Davis
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Gray
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Mansfield
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Ward
D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D017354:Point Mutation; D053764:Presenilin-1; D053766:Presenilin-2; D011487:Protein Conformation; D015398:Signal Transduction
D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2