Figure 3

Non-apoptotic roles of caspases in micropruning in plasticity and disease. (a) Caspases-9 and -3 along with XIAP, Bad, Bax and antiapoptotic Bcl2 has been shown to be involved in NMDA-R dependent AMPA-R internalization. Active caspase cleaves Akt to release the inhibition of GSK3β and LTD. Although cyt-c is released, whether it is required for Apaf1 function and whether the IBM proteins are needed, require clarification. (b) In Alzheimer’s disease (AD) presence of Aβ oligomers increases intrasynaptic Ca²⁺ levels to trigger caspase activation. C31 fragment derived from caspase cleavage and enzymatic processing of APP can block XIAP and further contribute to accumulation of active caspases. The requirement of cytochrome c and Apaf1 in the presence of Aβ oligomers is not known. This initial micropruning event can snowball into synaptic loss or dendritic branch loss and contribute to AD. The unknowns are represented by question marks. IBP, IAP binding motif proteins; Ca²⁺, calcium ions; Casp-9, caspase-9; Casp-3, caspase-3; Apaf-1, apoptotic protease activating factor 1; XIAP, inhibitor of apoptosis 1 on X; Aβ oligomers, amyloid beta oligomers; Akt, protein kinase B; GSK-3, glycogen synthase kinase 3; AMPA-R, AMPA receptor; NMDA-R, NMDA receptor; C31, C31 fragment of the amyloid precursor protein; LTD, long-term depression; APP, amyloid precursor protein