A Possible Path to Preventing TDP-43 Aggregation

TDP-43 is known to increase with age, and also forms aggregates observed in ALS and frontemporal dementia, among other conditions. The increased amount of TDP-43 alone, even without aggregates, appears to diminish the cellular housekeeping process of autophagy, with detrimental long term consequences. Artificially reducing the levels of TDP-43 too far will produce other issues, however, as this disrupts correct microglial function in the brain, making the microglia too aggressive when it comes to dismantling synaptic connections between brain cells. Thus building a therapy that targets TDP-43 isn't as straightforward as it might be. Here, researchers look at breaking down the aggregates rather than targeting TDP-43 indiscriminately, an approach that may result in a therapy for TDP-43-related conditions.

Scientists have long known that a protein called TDP-43 clumps together in brain cells of people with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's Disease, and is associated with neuron death. This same protein is thought to cause muscle degeneration in patients with sporadic inclusion body myositis (sIBM), leading many researchers to think that TDP-43 is one of the causative factors. Now, researchers found that a specific chemical modification called acetylation promotes TDP-43 clumping in animals. Using a natural anti-clumping method in mouse models, the scientists reversed protein clumping in muscle cells and prevented the sIBM-related muscle wea...

Source: Fight Aging! - July 19, 2017 Category: Research Authors: Reason Tags: Daily News Source Type: blogs