A study published in the journal Acta Neuropathologica
revealed that a protein accountable for safeguarding nerve cells, ATF5, can become implanted in other substances in the brains of patients with Huntington’s disease (HD).
Scientists from the Centro de Biología Molecular Severo Ochoain in Madrid conducted research that uncovered this process and its effects on preventing the protein from functioning properly. Additionally, the study found that areas where the protein are embedded can also contain clusters of the faulty huntingtin protein. The faulty protein can kill nerve cells and ultimately cause the disease.
HD is a neurodegenerative genetic disorder that typically present via motor, cognitive and psychiatric problems in a patient’s third or fourth decade of life. The disease progresses slowly, and current therapeutic options are limited to a management of symptoms. There are no approved therapies to specifically treat the neuronal deterioration associated with the condition.
The study, titled The Neuroprotective Transcription Factor ATF5 Is Decreased and Sequestered into Polyglutamine Inclusions in Huntington’s Disease
, worked primarily with ATF5 inclusions, or substances that are embedded in other substances, with the belief that these inclusions prevented protein from doing its job, leaving nerve cells more prone to rapid decline and eventually death.
By examining the brains of deceased patients, the researchers learned that the protein exists in the brains of both healthy patients and patients with HD. In the latter, however, it is confined to nerve-cell structures similar to those containing the detrimental huntingtin. It was demonstrated using different dyes resembling the different proteins that ATF5 had accumulated in the same spot as huntingtin.
Historical data says that ATF5 in mouse models acts to protect the nerve cells during epileptic seizures, and the new research shows that soluble ATF5 is crucial to cognitive function. Lower levels of it were found in key areas of patients’ brains, particularly the cortex.
The results concluded by the team of researchers insinuate that decreased ATF5 in HD reduces neurons that are more vulnerable to mutant huntingtin-induced apoptosis, nearly as much as sequestration into inclusions. Additionally, these findings suggest that ATF5-increasing interventions could potentially provide therapeutic options for HD.
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Hernandez IH, Torres-Peraza J, Santos-Galindo M, et al. Acta Neuropathol. Published online August 31, 2017. doi.org/10.1007/s00401-017-1770-2. Accessed November 14, 2017.