According to a story from hms.harvard.edu, a recent study is revealing new information about the connection between aging and neurodegenerative disorders, such as Parkinson’s disease, dementia, and amyotrophic lateral sclerosis. Neurodegenerative diseases typically involve the loss of neurons in the brain over time, which can lead to debilitating results for affected people.
Aging and Neurodegeneration
Over the years, as scientists have painstakingly researchers these menacing illnesses, a variety of potential risk factors have been discovered, including genetic mutations and viral infections. However, one of the most predominant risks that plays a role in all of these diseases is aging. As a whole, older people are almost always the ones affected by these diseases.
Precisely why aging is such a major risk for these illnesses is still not fully understood, but this latest study has recovered a more definite molecular connection between the effects of aging and the genetic origins of two neurodegenerative diseases: frontotemporal dementia and amyotrophic lateral sclerosis. These two diseases share some similarities in what causes them and what symptoms patients display.
About The Research
In both of these disorders, about one in every ten patients have a mutation which causes a protein called TBK1 to not function completely normally. The protein has been associated with neuroinflammation and programmed cell death in the past. In the study a group of mice were modified to reflect the reduced levels of TBK1 that are sometimes found in patients. Another group had their TBK1 suppressed entirely. The group with reduced levels were able to develop into normal mice, but the group with no TBK1 did not survive embryonic development.
It turned out mice of this last group could be saved if the activity of another protein called RIPK1 was blocked; TBK1 normally does this when it is present in normal amounts. The team also found another protein called TAK1 that also helped regulate the activity RIPK1. The TAK1 molecule plays a key role, and it tends to decline with aging. More importantly, TAK1 expression was even lower in patients with amyotrophic lateral sclerosis.
A new mouse model with reduced levels of both TBK1 and TAK1 revealed something remarkable. These mice began to display symptoms similar to a neurodegenerative disease. These mice had difficulty moving, did not respond to new environments well, and a reduced number of neurons.
The takeaway is that these two molecules both suppress RIPK1 activity, and even when one declines, the other can compensate. This could help explain why patients with TBK1 mutations don’t have issues until they get older and their TAK1 levels start to decline. The findings support the development of therapies that inhibit the activity of RIPK1. Read the original study here.