Neurodegeneration in C. elegans models of ALS requires TIR-1/Sarm1 immune pathway activation in neurons.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive and selective loss of motor neurons in the brain and spinal cord1. Numerous mechanisms have been associated with ALS including genes encoding the DNA/RNA-binding proteins TAR DNA Binding Protein 43 (TDP-43).
- elegans possesses an innate immune system that is induced in response to viral or microbial infection. One antimicrobial defence pathway in C. elegans consists of tir-1, encoding a Toll Interleukin 1 Receptor (TIR) domain adaptor protein. 4. In this study, transgenic C. elegans models for ALS were used to investigate the role of the innate immune response and discover that the TIR-1.
In the figure a Paralysis assay in liquid culture is shown. Twenty, adult day 4 worms expressing TDP-43 were transferred to M9 buffer and the numbers of movements were scored using a WMicrotracker (Phylumtech).
Nat Commun. 2015 Jun 10;6:7319. doi: 10.1038/ncomms8319.
As detected with an automated motility tracking system, TDP-43A315T; tir-1(qd4) animals showed improved swimming behaviour when placed in liquid culture compared to TDP-43A315T controls T controls (P<0.01, unpaired t-test)