Fig. 1
From: Drug development targeting degeneration of the basal forebrain cholinergic system: its time has come
β-CTF and/or α -synuclein induce Rab5-positive (early) endosomal swelling and dysfunction, which leads to a defect in endosome-mediated nerve growth factor (NGF) signaling. The resulting loss of trophic support provided by NGF leads to degeneration of cholinergic neurons in the basal forebrain, that downstream leads to dysfunction and eventual neurodegeneration in the cortex. Neflamapimod through inhibiting the kinase activity of p38α (an activator of Rab5) reduces Rab5 activity and reverses the endosomal pathology and cholinergic neuronal loss in the basal forebrain