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Fig. 7 | Translational Neurodegeneration

Fig. 7

From: Neddylation-dependent protein degradation is a nexus between synaptic insulin resistance, neuroinflammation and Alzheimer’s disease

Fig. 7

Neddylation-dependent IRS1 degradation is a nodal point in synaptic insulin resistance. Exposure to insulin results in phosphorylation of insulin receptors (InsR) (1) with subsequent activation of ATK/PKB (2). Both high amyloid load via stimulation of TNFα release from glia (3)  and MetS alter neuronal responsiveness to insulin (induce synaptic insulin resistance) as evidenced by reduced phosphorylation of InsR and the downstream effector AKT (4) and enhanced phosphorylation of IRS1. In parallel, synergism between MetS, high amyloid load and neuroinflammation promotes neddylation of CUL7 (5) and subsequent degradation of IRS1 (6)

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