The Role Of Proteasome Activity Change In The Toxicity Of PC12 Cells Induced By Manganese

[Background]Manganese is an essential trace element and it is required for many ubiquitous enzymatic reactions. But too much manganese can cause toxicity. The nerve system is particularly susceptible to this excess manganese. Chronic manganism can cause some extracorticospinal tract symptoms, which is similar to Parkinson's disease. Though there is some difference between manganism and Parkinson's disease in mechanism, manganese is now recognized as one of the major environmental risk factors for Parkinson's disease.The ubiquitin proteasome system (UPS) is the major system for intracellular protein degradation in eukaryotes, which is an important non-lysosome protein degrading channel. The UPS plays an important role in the regulation of cell cycle and the protein degradation connective to apoptosis. UPS can selectively degrade the aberrant and misprocessed proteins in eukaryotes. UPS controls the levels of most cytosolic and nuclear proteins, and keeps cell homeostasis. The last few years have seen increasing evidence for the involvement of the UPS in neurodegenerative disorders, especially sporadic PD. The substantia nigra of PD brain is abound with oxidized proteins, which are apt to accumulate, not easy to be degraded by UPS.In recent years, much more attention has been paid to the relationship between oxidative stress and neural degenerative diseases. Oxidative stress caused by iron, copper, manganese and other transition elements can elevate...