Gene Found that Regulates Protein Aggregates in Neurodegenerative Diseases
A gene called Ankrd16 can prevent the harmful protein aggregates that build up in neurological disorders, including Parkinson’s disease, according to researchers.
Their study, “ANKRD16 prevents neuron loss caused by an editing-defective tRNA synthetase,” published in the journal Nature, adds a new layer of knowledge about the underlying mechanisms involved in toxic protein aggregates, contributing to the understanding of neurodegenerative diseases.
Scientists have known that an accumulation of abnormal protein aggregates in the brain is key to the development and progression of several neurodegenerative diseases. But what causes this protein malfunction has been unclear.
University of California San Diego researchers led by Susan Ackerman, PhD, previously found that the cellular machinery responsible for translating genes into functional proteins could in part be responsible for this process.
This process serves as the editorial team of a newspaper: It carefully proofreads and controls the process of transforming the information contained within genes into functional proteins.
Small editing mistakes result in the incorrect insertion of a serine amino acid — the building blocks of proteins — into newly produced proteins, leading to “sticky” versions of proteins that will ultimately form toxic aggregates.
Specific cells in the cerebellum — a part brain of the brain that helps control movement and body balance — known as Purkinje cells are particularly sensitive to this disrupted process.
The research team has now found that the Ankrd16 gene is an important “proofreader” throughout this process and can prevent the faulty insertion of serine into protein sequences.
“Simplified, you may think of Ankrd16 as acting like a sponge or a ‘failsafe’ that captures incorrectly activated serine and prevents this amino acid from being improperly incorporated into proteins, which is particularly helpful when the ability of nerve cells to proofread and correct mistakes declines,” Ackerman said in a UC San Diego news story written by Mario Aguilera.
Purkinje cells normally have low Ankrd16 levels, which may explain why these nerve cells are more vulnerable to proofreading defects.
Increasing the levels of Ankrd16 in Purkinje cells from mouse models protected these cells from dying, while removing the gene led to an abnormal buildup of proteins and eventually cell death.
The researchers described Ankrd16 as “a new layer of the machinery that is essential to the prevention of severe pathologies that arise from defects in editing.”
