NPTX2 Involved in Neurodegeneration Driven by TDP-43 Aggregation

Altered, misfolded forms of TDP-43 are thought to contribute to neurodegeneration in a number of age-related conditions, primarily amyotrophic lateral sclerosis and frontotemporal dementia. As is the case for other misfolded proteins associated with neurodegeneration, aberrant TDP-43 may accumulate in much of the older population to levels sufficient to meaningfully contribute to cognitive decline. That TDP-43 has this negative impact is a relatively recent discovery, and in comparison to amyloid-β, tau, and α-synuclein little is known of the mechanisms by which TDP-43 aggregation causes dysfunction and death in brain cells. This doesn't stop the development of therapies that aim to clear forms of TDP-43, but it would be beneficial to have confirming data to demonstrate that the specific target is the right one. In today's research materials, scientists report on a step forward in understanding how aggregated TDP-43 causes cell death. There are no well-proven animal models of TDP-43 aggregation, in part because some of the details of TDP-43 pathology involve mechanisms specific to the human version of the protein, so the researchers built cell models in order to explore changes in cell function induced by the presence of TDP-43. They found a good candidate for further exploration in the form of NPTX2, a synaptic protein that appears to be upregulated to toxic levels in neurons affected by TDP-43 aggregation. It remains to be seen as to how this finding will progress ...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs