Protein Form Linked to Huntington's Disease Identified

A form of the protein that is linked to Huntington's disease influences the timing and severity of its symptoms, offering new avenues for treating not only this disease, but also a variety of similar conditions.

Scientists at the Gladstone Institute of Neurological Disease, (San Francisco, CA, USA) screened numerous antibodies that each bind uniquely to one type of misfolded huntingtin protein (Htt) in order to identify and tag each type. These antibodies acted as molecular tracking devices that are monitored with an automated microscope and specialized software. Experiments revealed that one of the antibodies, 3B5H10, bound to a form of Htt closely linked to neuron death and, therefore, disease progression.

Huntington's is an ultimately fatal disease that affects more than a quarter of a million people nationwide, is caused by mutations in the gene that creates the huntingtin, or Htt, protein. As the mutated gene produces Htt, a segment of the protein called polyglutamine is mistakenly expanded, distorting Htt's natural shape and function. As a result, the misfolded protein malfunctions and can be toxic.

Neuronal death is the key to the development of Huntington's symptoms, including erratic behavior, memory loss, and involuntary muscle movement. This study underscored the value of the cross-disciplinary work done at Gladstone while revealing techniques that scientists anywhere can apply to conditions involving misfolded proteins, such as Alzheimer's disease and type 1 diabetes.

Steven Finkbeiner, MD, PhD, a senior investigator at the Gladstone Institute said, "Effective treatments for diseases such as Huntington's and Alzheimer's have been slow to develop. We hope that our newfound understanding of precisely which misfolded proteins contribute to disease symptoms will speed up drug development for sufferers.” The study was published October 30, 2011, in the journal Nature Chemical Biology.

Related Links:
Gladstone Institute of Neurological Disease