Fig. 5

Proposed mechanism of action of the combined treatment with lenalidomide and CD5-D5. In the MBP-α-syn transgenic mouse model of MSA, oligodendrocytes produce high levels of α-syn, leading to the pro-inflammatory activation of microglia and astroglia. The diagram shows the mechanism of action of lenalidomide and LV-CD5-D5-ApoB in the MBP-α-syn transgenic mouse brain. The combined treatment with lenalidomide (Len) and LV-CD5-D5-ApoB (D5) reduces oligodendroglial α-syn accumulation, modulates astroglial activation, regulates the expression of cytokines, and activates the cytoprotective Akt signaling. Immunotherapy with LV-CD5-D5-ApoB may also target extracellular α-syn, promoting its uptake by microglial cells and reducing its incorporation into astroglial cells. The combined treatment also increases the expression of TNFα mRNA, which could be linked to the observed inhibition of ERK1/2 in favor of Akt signaling