Involvement of presenilin holoprotein upregulation in calcium dyshomeostasis of Alzheimer's disease.
Bottom Line: Here we report that the overexpression of PS1 full-length holoprotein forms, in particular familial Alzheimer's disease-causing forms of PS1, result in significantly attenuated calcium release from thapsigargin- and bradykinin-sensitive stores.Similarly, the knockdown of PEN-2 which is associated with deficient PS1 endoproteolysis and accumulation of its holoprotein form also leads to decreased ER calcium release.Taken together, the conditions in which the amount of full length PS1 holoprotein is increased result in reduction of calcium release from ER.
Affiliation: Department of Translational Brain Research, DZNE - German Center for Neurodegenerative Diseases, Munich, Germany.Show MeSH
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Mentions: To assess the physiological relevance of the finding that the accumulation of PS holoprotein is associated with the attenuated ER calcium release in the context of AD pathogenesis, we compared the PS1 holoprotein levels in the postmortem frontal cortices of FAD patients relative to non-demented control cases. As expected, the amount of PS1 holoprotein level in control individuals was relatively low. However we observed on average 1.7-fold significant increase in PS1 holoprotein levels in three FAD-PS1 patient cases. In contrast, the level of PS1 holoprotein in a FAD-APP patient was comparable to the controls (Fig. 4A and B). Table 1 summarizes the patient data from which the samples were collected.
Affiliation: Department of Translational Brain Research, DZNE - German Center for Neurodegenerative Diseases, Munich, Germany.