Promoting regeneration while blocking cell death preserves motor neuron function in a model of ALS.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a devastating and fatal neurodegenerative disease of motor neurons with very few treatment options. We had previously found that motor neuron degeneration in a mouse model of ALS can be delayed by deleting the axon damage sensor MAP3K12 or dual leucine zipper kinase (DLK). However, DLK is also involved in axon regeneration, prompting us to ask whether combining DLK deletion with a way to promote axon regeneration would result in greater motor neuron protection. To achieve this, we used a mouse line that constitutively expresses ATF3, a master regulator of regeneration in neurons. Although there is precedence for each individual strategy in the SOD1G93A mouse model of ALS, these have not previously been combined. By several lines of evidence including

SUBMITTER: Wlaschin JJ 

PROVIDER: S-EPMC10411937 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature