Integrative Neuroscience Topic 8: Huntington's Disease

When was HD first reported and when was the gene first identified?

It was first reported in 1872 and the first gene was identified in 1993.

Whats the most common way people get HD?

Dominantly inherited.

How is HD cured?

No cure. Treatment is given to make patients happy but only given when symptoms show.

What kind of people get HD?

Males and females.

Is HD fatal?

Yes. Death is due to complications of disease but not the disease itself.

What chromosome is HD found in?

On chromosome 4.

What causes HD

Expansion of CAG repeats in the huntingtin gene.

Can the environment cause HD to happen?

No this doesn’t contribute to someone having HD, it’s genetically inherited.

Huntingtins protein (HTT)

Large proteins associated with the plasma membrane.

It’s not restricted to neurons and happens everywhere. But most dense in the neurons.

Proposed functions of HTT

Essential for normal embryonic development.

Required in adult neurons for cell visibility.

Interacts with many proteins.

Involved in transcriptional regulation.

Describe the quality control for HD and how it relates to chaperones.

Ubiquitin is seen as a garbage disposal.

Chaperones are proteins that help other proteins fold correctly and stay functional. This is not a permanent fix. You need a lot of chaperones to keep up with all the misfolding that is happening.

What are the two mechanisms for mutant HTT aggregate formation based on expansion of polyQ?

The polar zipper model and the transglutaminase model.

They’re independent from one another.

Theoretical models.

The Polar Zipper Model

The normal tertiary protein conformation is destabilized by the presence of the polyQ tract.

The Transglutaminase Model

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