Cellular Maintenance Mechanisms Struggle to Break Down TDP-43 Aggregates, Leading to Neurodegeneration

The most common age-related neurodegenerative conditions are associated with the build up of various protein aggregates, chemically altered or misfolded proteins that can form solid deposits in and around cells when in that state. These protein aggregates are characterized by the ability to spread and grow, acting as seeds for more aggregation. They include the well known amyloid-β and tau of Alzheimer's disease, the α-synuclein associated with Parkinson's disease, and so forth. In recent years researchers have been devoting ever more effort to investigations of a less well known protein aggregate, TDP-43, associated with ALS and frontotemporal lobar degeneration. Today's open access paper is representative of work taking place to understand TDP-43 aggregates and how and why they form in the aging brain. The goal of research into protein aggregates is to either find a way to remove them, or to find a way to prevent them from forming in the first place. Protein aggregation is a feature of old people, not young people, despite the fact that the mechanisms that can give rise to aggregation are present throughout life. Thus the damage and change of aging, the rising dysfunction in near all cellular processes, is in some way involved in allowing the presence of protein aggregates to rise to pathological levels. In the research here, the finger is pointed at age-related impairment of the cellular housekeeping systems of the proteasome and autophagy, both of which will brea...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs