Upregulation of PSMB8 and cathepsins in the human brains of dementia with Lewy bodies.

Proteasome and lysosome are responsible for the homeostasis of proteins, lipids and carbohydrates in cells. Numerous reports indicate the proteolytic pathways have altered functions during neurodegeneration and aging. Dementia with Lewy bodies (DLB) is one of the leading forms of dementia, and the proteolytic alteration in DLB has not yet been fully investigated. This study shows that the components of proteasome and lysosome had selectively altered gene expression and enzymatic functions. Specifically, PSMB8, an inducible proteasomal β subunit, had elevated mRNA level and protein level in DLB brain compared with age-matched controls. The proteasomal caspase-like peptidase showed significant decreased activity in DLB brains and the trypsin-like/chemotrypsin-like activities did not reach statistical significance. Lysosomal cathepsin B and D had elevated mRNA levels while only cathepsin B showed elevated enzymatic activity in DLB brains. This data indicate that the alteration of proteolytic pathways is highly selective and comprehensive. Further study to elucidate the correlation between neurodegenerative development and the alteration of proteolytic pathways would be important for therapeutic development.