Huntington’s Disease: a domino effect triggered by mutant huntingtin.
Huntington’s disease (HD) is an inherited neurodegenerative disorder that causes progressive motor and cognitive dysfunction. The disease is caused by the expansion of a polyglutamine (polyQ) stretch in a protein named huntingtin. The most affected areas of the brain are corpus striatum and cortex (red arrows in the figure to the right), which explains the loss of motor control and the cognitive and psychiatric symptoms in HD patients.
The exact mechanism by which neurodegeneration occurs in HD is poorly understood. Neurons in HD brains are profoundly affected at multiple levels, from gene transcription to vesicle trafficking, cell signaling, energy metabolism and mitochondrial and synaptic function. It is not clear how mutant huntingtin affects so many aspects of the cell physiology. Most likely mutant huntingtin triggers a cascade of events or domino effect, where more and more cell functions become progressively impaired until the neurons die.