Proteasome overload is a common stress factor in multiple forms of inherited retinal degeneration.

ABSTRACT: Inherited retinal degenerations, caused by mutations in over 100 individual genes, affect approximately 2 million people worldwide. Many of the underlying mutations cause protein misfolding or mistargeting in affected photoreceptors. This places an increased burden on the protein folding and degradation machinery, which may trigger cell death. We analyzed how these cellular functions are affected in degenerating rods of the transducin γ-subunit (Gγ1) knockout mouse. These rods produce large amounts of transducin β-subunit (Gβ1), which cannot fold without Gγ1 and undergoes intracellular proteolysis instead of forming a transducin βγ-subunit complex. Our data revealed that the most critical pathobiological factor leading to photoreceptor cell death in these animals is insufficient capacity o

SUBMITTER: Lobanova ES 

PROVIDER: S-EPMC3683722 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature