SAN DIEGO — UC San Diego and Scripps Research Institute scientists announced Wednesday they have identified a gene that prevents harmful protein deposits, or “aggregates,” associated with neurological disorders such as Alzheimer’s and Parkinson’s disease.
Typically, the information transfer from gene to protein is carefully controlled, or biologically “proofread” and corrected. Abnormal aggregates can occur when cells fail to transmit proper genetic info to proteins, however, according to the researchers, who identified a gene called “Ankrd16” that rescues specific neurons — called Purkinje cells — that die when proofreading fails.
Without normal levels of Ankrd16, the nerve cells incorrectly activate an amino acid called serine that is then improperly incorporated into proteins that cause aggregation.
“Simplified, you may think of Ankrd16 as acting like a sponge or a `fail-safe’ 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,” said UCSD professor Susan Ackerman, the university’s Stephen W. Kuffler Chair in Biology.
Ackerman worked with UCSD colleague Markus Terrey, Scripps Research Institute scientists Paul Schimmel and My-Nuong Vo and other researchers on the Ankrd16 discovery. Their findings are published in Wednesday’s issue of the journal Nature.
Researchers describe Ankrd16 as “a new layer of the machinery essential for preventing severe pathologies that arise from defects in proofreading.”
In lab tests, elevating Ankrd16 levels protected Purkinje cells from dying, while removing Ankrd16 from other neurons in mice with a proofreading deficiency caused widespread buildup of abnormal proteins and ultimately neuronal death.
Few modifier genes of disease mutations such as Ankrd16 have been identified, according to the researchers. They said a modifier-based mechanism for understanding the underlying pathology of neurodegenerative diseases may be a promising route to understand how they develop.