The title of the paper that is reviewed is: “Sumoylation and Phosphorylation of α-synuclein”.
It is a research article that explores the molecular mechanism underlying αSyn toxicity. αSyn is a protein that is seen in the inclusion bodies of dopaminergic neurons in patients with Parkinson’s disease. Parkinson is an important neurodegenerative disease, and the cure of the disease is still unknown. In-depth understanding of the molecular pathogenic of the disease will help in determining suitable cure. Through the insight obtained from a literature review and previous studies, the authors identified that post translational modification of αSyn, could affect its physical characters like the ability to form aggregates, solubility in cytoplasm and its clearance from the cell. These physical properties of the αSyn are needed for the formation for neurotoxic inclusion bodies in dopaminergic cell. This is a significant topic, as understanding the molecular mechanism of αSyn action in disease, will help devise treatment strategies. Review of literature is presented in the introduction. It helps understand the different post translational modification in the protein and the role of the post translational modification in molecule to molecule cross talking. The literature review also helps to appreciate the significance of this work. The hypothesis have been made after a systematic study of literature and after identifying the knowledge gap that needs to be addressed. The research question of the study is: “Does crosstalk between specific post-translational modifications of αSyn modulates the processing of inclusions through degradation by autophagy or the proteasome?”
A molecular biological approach was used to prove the hypothesis. The study was conducted in yeast. Details of the yeast strain, plasmids used and transformation procedure are well explained. The technique used is explained in an organized and clear fashion. The information provided is sufficient to repeat the experiments and check their reproducibility.
The results are explained systematically and are relevant in addressing the hypothesis. The results identified that phosphorylation of S129 promotes αSyn ubiquitination. αSyn ubiquitination, helps decrease its stability. The results also suggest the inhibition of clearance of sumoylated Syn-α by the proteasome system. The discussion is well placed with the results. The differential post translational modification of αSyn helps regulate its activity in the cell. Nevertheless, its exact role in the cell is not yet known. Posttranslational modification does affect the physical property of the protein.
The study provides an evidence to support that post translational modification, do affect the pathway of protein degradation. The limitation of the study is that it is done in yeast and not in human cells. Though yeast may be the closest model for studying eukaryotic cell, there could be difference in post translational modification in human cells.
