Huntington’s disease, a late-onset neurodegenerative disorder characterized by issues with movement, mental function and behavior, presently has no cure. But a new research offers hope, as scientists have recognized a new therapeutic target for the disease.
The scientists, guided by Prof. Gillian Bates and peers from King’s College London, in cooperation with a team of international scientists, published the outcomes of their research in the journal PLOS Biology.
The gene for Huntington’s disease (HD), with respect to the scientists, was identified in 1993, and it has been puzzling the medical group ever since. It impacts roughly one person in 10,000, generally from about the age of 35, and the scientists observe that sufferers generally die within 20 years.
The role of the huntingtin protein in HD
Huntington’s disease is triggered by a strange mutation in a gene that encodes a protein known as “huntingtin.”
The scientists say these mutations then create long extends of glutamine – an amino acid – within the protein sequence, which stops huntingtin from folding effectively, making it “sticky.”
As an outcome of this, the huntingtin proteins clump jointly in the nucleus and the cytoplasm of cells, which interrupts facets of cellular function, resulting in the death of nerve cells.
These so-called huntingtin aggregates intervene with the transcription of genes, say the scientists, and other study has shown that suppressing a family of enzymes that control transcription – histone deacetylases (HDACs) – has valuable effects for HD. The issue is, however, that humans have 11 distinct HDAC enzymes, which makes understanding which HDAC to prevent very tricky.
HDAC4 decrease enhances movement, lifespan
Prof. Bates and her team performed their work in a mouse model with competitive Huntington’s disease, and they determined one of these enzymes – HDAC4 – as the target.
However, the scientists say that interestingly, all the action is happening in the cytoplasm and not the nucleus. And the role of HDAC4 in translation has little involvement. By sharing equally HDAC4 levels in the cells of HD mice, they identified they could postpone the clumping of huntingtin in the cytoplasm.
Furthermore, they noticed that reducing HDAC4 levels gets back the overall function of nerve cells and their synapses, generating developments in movement, neurological overall performance and even lifespan of the mice. The group adds that this all happens without any enhancement in the nucleus’ faulty gene transcription, which is in line with the cytoplasmic association between HDAC4 and huntingtin.
Significances for the future of Huntington’s disease
While the outcomes are very appealing, the scientists note that “it is still very beginning days and it is essential to note that the medical applications of any treatment coming up from this research have not been analyzed in a clinical setting.”
However, they do note that one inhibitor, suberoylanilide hydroxamic acid (SAHA), was formerly shown to enhance problems in the mouse model. This same inhibitor also reduces levels of the HDAC4 protein.e medical applications of any treatment coming up from this research have not been analyzed in a clinical setting. “The team is therefore optimistic that building HDAC4-targeted compounds could be a prospective technique to enhance the lives of HD patients.
When asked about any upcoming research, Prof. Bates informed:
“Our present focus is to dissect the connections between HDAC4 and huntingtin and to comprehend how a decrease in HDAC4 restores synaptic function and nerve cell connection in mouse models of Huntington’s disease.”