To understand the behavior of the brain and its development, a study on Mitochondrial Dynamics is necessary. Mitochondrial Dynamics include fission and fusion of dynamin-related proteins or (Drp1). These mitochondrial dynamics involve the fission of mitochondria, in which a mitochondrion divides, and mitochondrial fusion, in which mitochondria elongates. Though scientists are unclear about the proper relation between Drp1 and brain development, it can be said that activities or stimulants that affect the functioning of Drp1 have an influence on brain development as well.
New Protein Discovered: An Isoform Of Senp5
To treat brain development disorders and other types of diseases like degenerative neurological diseases, it is necessary to understand the process that is involved in brain development.
Mitochondrial dynamics, which are subcellular structures involved in cellular energy metabolism, is the primary process involved in brain development. These processes are facilitated by the differentiation of neurons or also can be referred to as brain cells, which start from the embryonic stage. In a recent study, a group of scientists led by Professor Shini-Ichi Sakakibara from Waseda University has discovered a protein that helps in regulating the Drp1, which has an effect on brain functioning. Sakakibara said that neurological disorders like Alzheimer’s and Parkinson’s are primarily caused by a process called SUMOylation. Studies show that SUMOylation plays a key role in causing these disorders. SUMOylation is actually a modification undergone by Drp1. The new protein discovered affects the SUMOylation process, which scientists have found as a likable option for treatments and therapies related to disease caused by SUMOylation.
Right after making Drp1 proteins, they are modified by another protein called small ubiquitin-like a modifier (SUMO). The human body tags the Drp1’s which are later SUMOylated, for degradation. To control the number of proteins that are being degraded, the tagged Drp1’s are untagged by the body. The process involved is called DeSUMOylation. According to a previous research release, SUMO- specific protease 5 (Senp5) enzyme acts as a catalyst for deSUMOylation. This variant helping in deSUMOylation is called Senp5L and it helps in breaking the bond between Drp1 and SUMO. In the study conducted, the scientists have discovered a new variant of the Senp5 enzyme and named it Senp5S. The research team carried out in vitro experiments utilizing cell traces and in utero experiments using mouse embryos to research the effects of Senp5 and SUMOylation involved in mitochondrial dynamics and neuronal differentiation (brain cells). The research team has found that Senp5S does not break the bond between Drp1 and SUMO unlike Senp5L, which is coined as peptidase activity. However, it is found that Senp5S competes with the Senp5L at the reaction site and prevents the bond breaking between Drp1 proteins and SUMO (deSUMOylation), and also regulates the mitochondrial dynamics that help in brain development. Further studies on the isoform revealed that balance between SUMOylation/ deSUMOylation affects the mitochondrial structure and endoplasmic reticulum. The endoplasmic reticulum is a cellular structure that helps in protein production, which is found to affect balance.
Sakakibara said that a balanced amount of both Senp5L/ Senp5S is necessary and essential for brain development. Their studies suggest the vital role of pre-translational SUMOylation in the process of brain development and neuronal differentiation. It helps to understand the importance of SUMOylation that happens in the brain.
The Discovery of this new isomer may pave a new path to the pathology department to cure disorders caused by the SUMOylation and other neurological disorders, which could help in finding new and effective ways of therapies and treatments to cure diseases like Alzheimer’s and Parkinson’s.
