Furthermore, these plant metabolites improved the lysosomal autophagy process by increasing the expression levels of Beclin-1, LC3II and cathepsin B genes for clearance of Aβ and NFT, and increased the expression of transporter proteins, P-glycoprotein (P-gp) and low density lipoprotein receptor-related protein-1 (LRP-1) for the clearance of Aβ load from brain across the blood-brain barrier (BBB) as well as increased the expression of PPAR-γ and ApoE proteins for clearance of Aβ in ApoE mediated pathway from brain.
Moreover, cathepsin B in secretory vesicles has been recently identified as a β-secretase for production of neurotoxic β- amyloid (Aβ) peptides that accumulate in Alzheimer's disease (AD), participating as a notable factor in the severe memory loss in AD.
In this issue of Neuron, Mueller-Steiner et al. manipulate the expression of cathepsin B in aged APP transgenic mice, observing that increased expression degrades preformed oligomeric and fibrillar amyloid, while inactivation accelerates beta-amyloidosis.