A series of studies conducted by researchers from Cornell University reveals a strong potential cause of amyotrophic lateral sclerosis (ALS): protein clumping.
In a media release published in Cornell University website on Thursday, October 23, three chemists have worked on a series of studies that aimed to pinpoint the relationship between a certain type of protein activity and the development of ALS.
Chemistry and Chemical Biology professor Brian Crane was the lead author of the first study and acted as a co-author on a follow-up that involved a technology called spectroscopy. Crane and Jack Freed, who works as a physical chemistry professor of the said university, then collaborated with National Biomedical Center for Advanced ESR Technology associate director Petr Borbat.
The first study revolved around the concept and use of a special type of spectroscopic method called pulsed dipolar ESR (electron spin resonance). It was later published in Biophysical Journal on October 7. Seven days after, they released a follow-up paper, in collaboration with researchers from Scripps Research Institute, this time focusing on the use of the technology in establishing the relationship between protein aggregation and symptoms of ALS. It appeared in PNAS on October 14.
Based on their studies and using the technology, they discovered that the destabilization of the protein structure of SOD1 can be one of the main causes for the degeneration of the neurons that then leads to the development of ALS. SOD1 is rich in copper, which acts as a protective shield against these neurons so they don't suffer from oxidative damage.
The protein structure undergoes certain mutations, which then leads to heightened protein motions and then aggregation or clumping, which is definitely not great for any healthy cell.
Although there were already prior studies that established the link between ALS and SOD1 mutations, they weren't able to properly pinpoint the differences between the mutated and normal protein structures. The technology used by these Cornell University chemists for the first time established such differences as they were able to see how these proteins interact or communicate with one another and how mutations are directly correlated to the degree ofALS symptoms.