20S proteasome mediated degradation of DHFR: implications in neurodegenerative disorders |
| |
Authors: | Amici Manila Sagratini Danila Pettinari Assuntina Pucciarelli Stefania Angeletti Mauro Eleuteri Anna Maria |
| |
Institution: | Department of Molecular, Cellular and Animal Biology, Post-Graduate School in Clinical Biochemistry, University of Camerino, 62032 Camerino (MC), Italy. |
| |
Abstract: | The 20S proteasome is responsible for the degradation of protein substrates implicated in the onset and progression of neurodegenerative disorders, such as alpha-synuclein and tau protein. Here we show that the 20S proteasome isolated from bovine brain directly hydrolyzes, in vitro, the dihydrofolate reductase (DHFR), demonstrated to be involved in the pathogenesis of neurodegenerative diseases. Furthermore, the DHFR susceptibility to proteolysis is enhanced by oxidative conditions induced by peroxynitrite, mimicking the oxidative environment typical of these disorders. The results obtained suggest that the folate metabolism may be impaired by an increased degradation of DHFR, mediated by the 20S proteasome. |
| |
Keywords: | 20S proteasome Dihydrofolate reductase Neurodegenerative pathologies Oxidation |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|