Proteasome Inhibition, Parkinson’s Disease

Definition

Proteasomes are large intracellular protein complexes whose main function is to degrade misfolded or damaged proteins by proteolysis. Consequently, proteasomes assist cells in regulating the concentration of particular proteins and degrade unwanted proteins via its inherent protease activity. Eukaryotic proteasome has both nuclear and cytoplasmic localization. The most common form of the proteasome is the 26S proteasome, which contains one 20S core particle structure. The core is hollow and provides an enclosed cavity in which proteins are degraded. Initially, cellular proteins targeted for degradation are tagged with several molecules of a small protein marker called ubiquitin thus generating a polyubiquitin chain through a three-step enzymatic cascade. This polyubiquitin chain is bound by the proteasome, allowing it to degrade the tagged protein. Upon recruitment to the proteasome, the substrates must be unfolded to pass through the narrow barrel of the proteasome where...