Targeting autotaxin impacts disease advance in the SOD1-G93A mouse model of amyotrophic lateral sclerosis.

A preclinical strategy to broaden the search of potentially effective treatments in amyotrophic lateral sclerosis (ALS) relies on identifying factors controlling motor neuron (MN) excitability. These partners might be part of still unknown pathogenic pathways and/or useful for the design of new interventions to affect disease progression. In this framework, the bioactive membrane-derived phospholipid lysophosphatidic acid (LPA) affects MN excitability through LPA receptor 1 (LPA ).

Interfering with lysophosphatidic acid receptor edg2/lpa signalling slows down disease progression in SOD1-G93A transgenic mice.

Aims: Alterations in excitability represent an early hallmark in Amyotrophic Lateral Sclerosis (ALS). Therefore, deciphering the factors that impact motor neuron (MN) excitability offers an opportunity to uncover further aetiopathogenic mechanisms, neuroprotective agents, therapeutic targets, and/or biomarkers in ALS. Here, we hypothesised that the lipokine lysophosphatidic acid (lpa) regulates MN excitability via the G-protein-coupled receptor lpa .