Protease activity in the aging brain

Abstract

There is abundant evidence for the accumulation of damaged and misfolded proteins in the aging mammalian brain. This accumulation may result from an increasing burden of oxidative damage combined with a diminished capacity to degrade aberrant proteins through the lysosomal and proteasomal pathways (the two major systems for the regulated disassembly of proteins). A chronic proteolytic deficit in either or both systems is predicted to lead to a neurotoxic crisis that has been described as garbage catastrophe. The evidence for the decline in proteolytic capacity of the degradative systems and the hypothesized events leading up to their catastrophic failure are reviewed. © 2007 Springer-Verlag US.