Molecular Link Discovered Between Aging and ALS, Frontotemporal Dementia

This is the Medscape Neurology Minute. I am Dr Alan Jacobs.

Researchers from Harvard Medical School have published a study^[1] analyzing the links between aging and neurodegeneration. They based their research on the fact that 10% of patients with both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia have a mutation affecting expression of a protein involved in programmed cell death called TBK1.

They created transgenic mice with both genes for TBK1 knocked out, which was lethal prenatally. Interestingly, though, the mice without any TBK1 were able to fully rescue and lead healthy lives by blocking the activity of another important cell-death-mediated protein, called RIPK1.

It turns out that TBK normally functions to inhibit RIPK1 during embryonic development. This fact led the researchers to study TAK1, another inhibitor of RIPK1, which significantly declines with age in the human brain. The researchers bred mice expressing half-normal amounts of TAK1 and TBK1. These mice developed motor deficits, anxiety behavior, motor neuron dysfunction, and cell death. Yet, when they inhibited RIPK1, they observed a reversal in symptoms.

The authors concluded that RIPK1 inhibitors, which are now under development, may help patients with ALS and frontotemporal dementia.

This has been the Medscape Neurology Minute. I am Dr Alan Jacobs.

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Cite this: Alan R. Jacobs. Molecular Link Discovered Between Aging and ALS, Frontotemporal Dementia - Medscape - Dec 07, 2018.