“Guardian” may protect brain against neurodegeneration
Original article: Tet3 reads 5-carboxylcytosine through its CXXC domain and is a potential guardian against neurodegeneration, Cell Rep: January 26, 2016
A protein in the brain, TET3FL, may guard against neurodegeneration by keeping cellular “trash removal” processes running smoothly.
Why is it important?
The findings lay the groundwork for new investigations into TET3FL and how it may be harnessed for new Parkinson’s therapies.
“While it is well known that aging is a major factor for Parkinson’s, little is known about why this is the case. This study has identified a mechanism which could explain the age-related increase in Parkinson’s by pointing to an enzyme that helps keep age-related DNA changes (especially those controlling garbage disposal in cells) in check and suggests that this enzyme is reduced in activity as part of normal aging.” Dr. Patrik Brundin
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Much like sticky grains of rice, abnormal alpha-synuclein proteins clumps together, forming the Lewy bodies found in the brains and nervous systems of people with Parkinson’s. It is thought that the cell’s inability to clean out these proteins causes inflammation and, ultimately, damage or death to the cell. When enough of the dopamine-producing cells in the brain are damaged or killed, Parkinson’s hallmark movement problems begin.
The study centers in part on epigenetics—the set of controls that regulate how genes are expressed without actually changing the genetic instruction manual itself. TET3FL appears to help ensure these controls work properly, ultimately guarding against errors that could be harmful.
The majority of genes associated with Tet3FL are part of pathways which are responsible for clearing out old and damaged proteins and other cellular components. Mutations in one of these genes, GBA, are recognized as strong genetic risk factors for developing Parkinson’s. Knowing how genes like GBA are regulated could help with the development of novel treatments for Parkinson’s.
Epigenetic research may also be critical for identifying biomarkers of Parkinson’s which are greatly needed for early diagnosis, as well as for the prediction of disease progression and treatment outcome. Emerging reports indicate that certain epigenetic differences observed in the Parkinson’s brains are detectable in more easily accessible tissues.
Original article: Jin SG, Zhang ZM, Dunwell TL, Harter MR, Wu X, Johnson J, Li Z, Liu J, Szabó P, Lu Q, Xu G, Song J, Pfeifer GP. January 26, 2016. Tet3 reads 5-carboxylcytosine through its CXXC domain and is a potential guardian against neurodegeneration. Cell Rep.