Final Answer:
The two main factors contributing to the pathogenesis of Huntington's disease (HD) are genetic mutations involving the HTT gene and the subsequent production of abnormal huntingtin protein.
Step-by-step explanation:
Huntington's disease, a neurodegenerative disorder, primarily stems from genetic mutations in the HTT gene. This gene is responsible for encoding the huntingtin protein. In affected individuals, there's an abnormal repetition of CAG nucleotide sequences within the gene. This repeated sequence leads to the production of a mutated form of the huntingtin protein, which becomes toxic to neurons in specific regions of the brain, particularly the basal ganglia.
The number of CAG repeats in the HTT gene is directly correlated with the age of onset and severity of HD. A higher number of CAG repeats results in an earlier onset and more severe symptoms. For instance, individuals with 40 or more CAG repeats typically develop symptoms earlier in life and experience a more aggressive form of the disease.
Furthermore, the mutant huntingtin protein disrupts various cellular processes, causing neuronal dysfunction and ultimately neuronal death. This disruption leads to the progressive loss of motor control, cognitive decline, and psychiatric disturbances characteristic of Huntington's disease. Understanding these genetic and protein-related factors is crucial for advancing research and developing potential therapies aimed at targeting the underlying mechanisms of HD.