Researchers at the Perelman School of Medicine at the University of Pennsylvania found that with years neurons or nerve cells failed to perform the activity they could have when they were younger. The team explains that normal cells secretes proteins and other "garbage" or "garbage" through the autophagy process. The cell thus releases dysfunctional proteins and aggregates of unused proteins.
As cells grow, this mechanism fails, and since nerve cells do not replicate, the protein strives to accumulate within them. This could increase the risk of developing neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis), Alzheimer's and Parkinson's disease, researchers say. The study appeared in the latest issue eLife and was named: "Expression of WIPI2B suppresses the fall in autophagosomic biogenesis in neurons."
Aberrant auto-phagosomes accumulate in neurons of the older mouse (Credit: Andrea Stavoe, Penn Medicine, eLife)
The team used live cell recordings or "double marking autophagosic biogenesis" of neurons taken from young and old mice. Principal authors dr.sc. Erika Holzbaur, professor of physiology, and Dr. Andrea Stavoe, Postdoctoral Associate at the Holzbaurve Laboratory, explain that the autophagy process in the purification of protein residue remains a discovery of 2016 that has captured its discoverers. The Nobel Prize for Physiology and Medicine in 2016. Researchers were Pallavi Gopal from Yale University and Andrea Gubas and Sharon Tooze of the Francis Crick Institute from London.
The team wrote: "Young neurons seem to efficiently purify dysfunctional organelles and protein aggregates, but several studies have investigated autophagy in the old neurons. Since age is the most important common risk factor in neurodegenerative diseases, explaining how autophagy changes neurons with the age, it is crucial for understanding neurodegenerative diseases. "The danger to the environment What motivates our research line is that most neurodegenerative diseases involving improper autophagy, such as ALS, and Alzheimer's, Huntington's, and Parkinson's disease, are also an aging disorder.
Researchers have written that autophagy (auto-self-phagy-eating) begins with the development of autophagy within the cell. This self-refocus is eaten with damaged structural proteins, misfolded proteins that would not use cells and structures to be demolished and degraded. These protein proteins are then sequenced in a "biological trash bag" until the autophagosus is coupled to the lysomom inside the cell. Lysosom contains enzymes that are potent and can break the protein and other garbage and also recycle reusable materials. So the cell is cleansed from the remains. The team writes: "Biogenesis of autophagy, stored from yeast to humans, involves over 30 proteins acting in different protein complexes to encompass either the mass cytoplasm or the specific load within the double membrane."
In the event that this process fails, there will be accumulation of rubbish in the cells and this can eventually kill neurons or nerve cells, the researchers explain. Stavoe said, "Think about the city streets during the strike of workers in sanitary facilities."
In their research, the team evaluated mouse neurons during the aging process. They noted that with the years there was a significant reduction in autophagy production. Autophagys that occurred in older neurons also had prominent shortcomings. These reduced numbers and deformed autophagys led to the buildup of protein residues within the neuronal mice. Stavoe added that brain donors have shown that people with neurodegenerative disorders have similar deformed fewer auto-phagocytes.
The researchers noted that one of the proteins called WIPI2B in older mice, when included, could help older mice produce sufficient autofagosomas. This means that the whole process of extracting garbage from the protein returns to the right path, the researchers wrote. The team focused on the activation of this protein and added that this could help in the biological regulation of autophagy creation. Stavoe said, "This astonishing and fully salvage of autophagy by one protein suggests a new therapeutic goal for aging associated with neurodegeneration." autofagosoma.
The authors concluded: "Finally, we showed that auto-phagocyte biogenesis speed decreased in neurons during aging, but we reduced this reduction by over-expression of one component of autophagy, WIPI2B."
The research was funded by the NIH scholarship for independence and the Javits NINDS award.
Andrea KH Stavoe, Pallavi P Gopal, Andrea Gubas, Sharon A Tooze, Erika LF Holzbaur. /elifesciences.org/articles/44219