Upregulation of proteasomal/lysosomal components in the human brains of dementia with Lewy bodies
Qunxing Ding and Haiyan Zhu
Department of Biological Sciences, Kent State University at East Liverpool
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 of DLB.