[Study on the mechanism of Alzheimer disease-related gene presenilin-1].
OBJECTIVE
To study the pathogenic mechanism of Alzheimer disease-related gene presenilin-1 (PS-1) mutation causing AD.


METHODS
Four neural cells, including SY5Y cell, transgenic cells harboring PS-1 mutation, wild-type PS-1 and lipofectin were measured for neuronal Ca(2+) homeostasis and cell apoptosis. Intracellular calcium antagonist and antioxidant, such as Ginaton and nimodipine, were used in cultured neural cell and neuronal Ca(2+) level and cell apoptosis were examined.


RESULTS
Elevation of intracellular calcium level and cell apoptosis induced by amyloid beta-peptide (Abeta) were enhanced in PS-1 mutation cell, as compared with others cells (P < 0.01). Intracellular calcium antagonist and antioxidant could inhibit apoptosis and decrease intracellular calcium level for PS-1 mutation (P > 0.05). There was significant correlation between the percentage of apoptosis and intracellular calcium level for PS-1 mutation.


CONCLUSIONS
The pathogenic mechanism of PS-1 gene mutation causing AD was PS-1 mutation enhancing apoptosis by intracellular calcium overload. Intracellular calcium blocker and antioxidant could decrease intracellular calcium overload and inhibit apoptosis.
D000368:Aged; D000544:Alzheimer Disease / Q000209:etiology / Q000235:genetics*; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D053764:Presenilin-1
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D002118:Calcium