A new study, carried out by researchers from the University of British Columbia, has demonstrated that a strict dietary schedule may be beneficial to patients with neurodegenerative disorders.
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder. It is caused by mutations in the Huntingtin (HTT) gene. The protein encoded by the HTT gene is also called Huntingtin (HTT)
. Until now, little is known about the accurate functions of HTT protein. But evidence suggests that HTT protein plays a key role in neurons in the brain. In patients with HD, mutations in the HTT gene leads to the production of an altered form of HTT protein, called mutant Huntingtin protein (mHTT).
At present, there is no cure for HD. Research on the pathogenesis of HD is on going. mHTT has been found to negatively affect multiple cellular activities. Thus, removing mHTT represents a potential way to treat the disease. There are two possible approaches to remove mHTT: 1) lowering HTT RNA, and 2) increasing degradation of mHTT protein. Recent studies have suggested that both soluble and aggregated forms of mHTT are cleared through autophagy and that HTT plays a role in the regulation of autophagy.
Simply put, autophagy is a process in which unnecessary or dysfunctional cellular components are degraded inside the cell. This degradation mechanism is essential for basal homeostasis, various cellular functions, and the survival of cellular organisms. Impaired autophagy has been seen in many human diseases.
The primary goal of the new study is to investigate the connection between mHTT cleavage and autophagy. To achieve this goal, the researchers used mouse models of HD that express full-length mHTT. They stimulated autophagy by restricting access to food in HD mice. The results showed that both fasting and scheduled feeding induce autophagy in the brains of HD mice. Furthermore, the amounts of mHTT protein in the brain are remarkably reduced.
mHTT levels are strongly associated with the pathogenesis of HD. These results "imply that mHTT clearance could be enhanced by a regulated dietary schedule that promotes autophagy." More research is needed to better understand the beneficial effects of nutrient deprivation on neurodegenerative disorders like HD.
According to the researchers, it has been known for a while that some aspects of autophagy don't work properly in HD patients, and now the new study demonstrates in mice that fasting or a regulated eating schedule can increase the autophagy mechanism, which in turn help lower levels of the harmful mHTT proteins in the brain. So, a modified dietary schedule may be beneficial to patients with HD.
The full paper, titled "Preventing mutant huntingtin proteolysis and intermittent fasting promote autophagy in models of Huntington disease," can be read in the journal Acta Neuropathologica Communications.