THESIS
2016
vii, 45 pages : illustrations ; 30 cm
Abstract
α-Synuclein (α-syn) is the major component of Lewy bodies (LBs), a neuropathological hallmark of Parkinson’s disease. The abnormal levels of α-syn caused by an imbalance between α-syn synthesis, aggregation, and clearance may be toxic and a key to the pathogenesis of PD. Phosphorylation of α-syn plays a significant role in α-syn aggregation. And the Ser-129-phosphorylated α-syn (pS129 α-syn) is the most common synuclein modification (~90%) observed in LBs. However, the role of pS129 α-syn in the biogenesis of LBs remains unclear. Here, we reported that Polo-like kinase 2 (PLK2), an important kinase in α-syn phosphorylation at Ser129, interacted with, phosphorylated and enhanced α-syn autophagic degradation in a kinase activity-dependent manner. In HEK293T cells, ubiquitin-proteasome sys...[
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α-Synuclein (α-syn) is the major component of Lewy bodies (LBs), a neuropathological hallmark of Parkinson’s disease. The abnormal levels of α-syn caused by an imbalance between α-syn synthesis, aggregation, and clearance may be toxic and a key to the pathogenesis of PD. Phosphorylation of α-syn plays a significant role in α-syn aggregation. And the Ser-129-phosphorylated α-syn (pS129 α-syn) is the most common synuclein modification (~90%) observed in LBs. However, the role of pS129 α-syn in the biogenesis of LBs remains unclear. Here, we reported that Polo-like kinase 2 (PLK2), an important kinase in α-syn phosphorylation at Ser129, interacted with, phosphorylated and enhanced α-syn autophagic degradation in a kinase activity-dependent manner. In HEK293T cells, ubiquitin-proteasome system (UPS)-mediated increase in PLK2 levels enhanced the degradation of α-syn via Autophagy-lysosome pathway (ALP). Moreover, we showed that PLK2 can be modified by S-nitrosylation, a reversible post-translational modification of proteins, in vitro by NO donor and in vivo by endogenous NO source. This modification weakened the capability of PLK2 to phosphorylate
α-syn. Taken together, this study demonstrates that PLK2 is able to modulate α-syn and its degradation in a kinase activity-dependent manner.
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