Involvement of presenilins in cell-survival signalling pathways.
Familial AD (Alzheimer's disease) is a rare autosomal dominant form of AD, associated with clinical and pathological features similar to those identified in the more prevalent sporadic AD cases. The majority of familial AD cases are caused by mutations in either of the highly homologous PS (presenilins), an essential component of the gamma-secretase enzyme complex, or amyloid precursor protein, a gamma-secretase substrate and the precursor of amyloid beta peptides. The observation that PS are absolutely required for gamma-secretase activity, and parallel studies demonstrating that PS interact with several signalling molecules, modulate their stability or regulate their proteolysis, have led to the suggestion that involvement of PS in additional signalling pathways mediating key cellular functions may contribute to the pathogenesis and progression of neurodegeneration. In this paper, we review PS-regulated molecules, their role in cell signalling and possible involvement in neurodegeneration in patients suffering from AD.
McCarthy
J V
JV
Signal Transduction Laboratory, Biochemistry Department, Biosciences Institute, University College Cork, Cork, Ireland. jv.mccarthy@ucc.ie
D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D016282:Aspartic Acid Endopeptidases; D001665:Binding Sites; D002470:Cell Survival; D010450:Endopeptidases / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D053764:Presenilin-1; D053766:Presenilin-2; D011485:Protein Binding; D015398:Signal Transduction / Q000502:physiology*
D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human