Researchers have found that Huntington's disease may progress to advanced stages more because of a degradation of the cells' health maintenance systems than because of increased damage from the disease pathology itself.
Loss of cellular homeostasis has been implicated in the etiology of several neurodegenerative diseases (NDs). Using a novel computational approach to integrate dimensional RNA-seq and in vivo neuron survival data, investigators map the temporal dynamics of homeostatic and pathogenic responses in four striatal cell types of Huntington’s disease (HD) model mice.
This map shows that most pathogenic responses are mitigated and most homeostatic responses are decreased over time, suggesting that neuronal death in HD is primarily driven by the loss of homeostatic responses. Moreover, different cell types may lose similar homeostatic processes. HD relevance is validated by human stem cell, genome-wide association study, and post-mortem brain data.
"These findings provide a new paradigm and framework for therapeutic discovery in HD and other NDs", said the author.
Source: DOI: 10.7554/eLife.64984