According to a publication from Laboratory Equipment, a new animal study of mice with simulated Huntington’s disease suggests that a protein associated with the symptoms of Huntington’s can form small, sticky “nanotubes” that protrude from and link neurons together.
The study, conducted by Scripps Research, also observed mutated huntingtin proteins linked to development of Huntington’s disease traveling along these nanotubes from cell to cell, hinting at how the disease might progress in humans.
About Huntington’s Disease
Huntington’s disease (HD) is a rare genetically-inherited condition that causes the progressive breakdown of neurons (nerve cells) in the brain.
A mutated form of the HTT gene provides instructions to produce a mutant form of the protein huntingtin. Normally, huntingtin is an essential protein whose exact role is unclear (appearing to play an important role in neural health and prenatal development) but of vital importance. The mutated form of huntingtin, however, is highly unstable and linked to the breakdown of neurons over time (thus Huntington’s disease).
As a patient’s neurons deteriorate, they may experience any number of physical and neurological symptoms. They may have difficulty speaking, and might develop muscle rigidity, abnormal eye movement, or involuntary twitching movements called chorea. Certain observable changes in behavior (confusion, promiscuity, proneness to outbursts) and psychiatric disorders (especially depression) are also strongly associated with the disease.
Very rarely HTT can mutate spontaneously in an individual with no family history of Huntington’s disease. The majority of cases, however, are inherited.
Rhes Protein Seems to Form “Tunnel-Like” Protrusions
Rhes is an enzyme (most of which are proteins) that is strongly expressed in a part of the brain called the striatum. Specifically, it’s a small GTPase, a type of enzyme that catalyze the reaction of guanosine triphosphate (GTP) to guanosine diphosphate (GDP). GTP is a nucleotide that plays a vital role in signal transmission between cells. It can also occasionally can act as a source of cellular energy, and is a building block of RNA during transcription.
However, despite their important function, the new Scripps Research study suggests that Rhes might be responsible for the cytotoxicity of mutant huntingtin proteins.
Huntingtin, even in its mutant form, is found throughout the body in varying concentrations. However, Huntington’s disease is characterized by the degeneration of nerves in the brain specifically – especially the striatum. The thinking is that mutant huntingtin might only be toxic in the presence of some other substance – and scientists think that other substance could be the Rhes protein.
Evidence has been lacking, however – until now.
The Scripps study, headed by associate professor Srinivasa Subramaniam, found that in mouse neurons, Rhes proteins form “sticky, string-like protrusions.” Manish Sharma, first author on the study, called the protrusions “tunnel-like.”
When mutant huntingtin was stained and introduced to the mouse neurons, Subramaniam and Sharma watched the protein travel from neuron to neuron through the tunnels Rhes made.
The study, it should be noted, is not necessarily final in its conclusions. Animal studies, though frequently relied upon in such cases, are no guarantor of similar findings in humans. It does, however, provide an intriguing and plausible explanation for the way Huntington’s progresses.
What do you think of this exciting study? Does the fact that it was an animal study limit your hopes for results in humans? Patient Worthy wants to hear from you!