FIG. 3.

Intracellular signaling pathways involved in ER calcium overload at AD. Possible mechanisms involved in ER Ca²⁺ overload in AD. (i) FAD-associated mutations cause disruption of passive Ca²⁺ leak function of PSs, thus causing accumulation of Ca²⁺ in the ER lumen. (ii) Aβ potentiates plasma membrane Ca²⁺-permeable channels, leading to the increase of cytosolic and ER Ca²⁺ content. (iii) PS1 may interact with SERCA pump via direct protein–protein interaction, thus potentiating its Ca²⁺ pumping activity. AD, Alzheimer's disease; ATPase, adenosine triphosphatase; FAD, familial form of Alzheimer's disease; PS, presenilin; PS1, presenilin 1; SERCA, sarco/endoplasmic reticulum Ca²⁺-ATPase. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars