Figure 1.

Links between Alzheimer’s disease (AD) and ubiquitin-proteasome-mediated degradation. The figure depicts the pathogenesis of AD and the resultant synaptic/cognitive dysfunction via Aβ and tau, the two main postulated mechanisms of AD. The connections between the ubiquitin-proteasome pathway (UPP) and the components of the two pathways are indicated. Only key relevant features of AD pathogenesis are shown. Processes with a purely inhibitory effect are shown by red connectors. Negative regulatory mechanisms with potential for therapeutic intervention are shown by purple connectors. APP, amyloid precursor protein; s-APPβ, soluble N-terminal APP fragment; PDE3, phosphodiesterase 3; PKA, Protein Kinase A (cAMP-dependent protein kinase); Ub-tau, tau with attachment of many ubiquitin (Ub) molecules (i.e., polyubiquitinated tau); stars indicate phosphorylation; shapes with filled red circles with tails represent polyubiquitin attachment. Created with http://biorender.com/.