Obesity and the Ageing Brain: Could Leptin Play a Role in Neurodegeneration?

Figure 1

Signalling downstream of leptin binding to the Ob-R receptor. A number of pathways are activated. JAK-2-mediated phosphorylation of Tyr₉₈₅ on Ob-Rb activates SHP2 and subsequently ERK. Phosphorylation of Tyr₁₀₇₇ and to a lesser extent Tyr₁₁₃₈ activates STAT5, whilst phosphorylation of Tyr₁₁₃₈ activates STAT3. Activation of STAT transcription factors leads to alterations in gene expression. The biochemical pathways leading to activation of PI3kinase, AMPK, and mTOR when leptin binds Ob-Rb are less well characterised.