OMICS-BASED EXPLORATION AND FUNCTIONAL VALIDATION OF NEUROTROPHIC FACTORS AND HISTAMINE AS THERAPEUTIC TARGETS IN ALS

Abstract A plethora of genetic and molecular mechanisms have been implicated in the pathophysiology of the heterogeneous and multifactorial amyotrophic lateral sclerosis (ALS) disease, and hence the conventional “one target-one drug” paradigm has failed so far to provide effective therapeutic solutions, precisely because of the complex nature of ALS. This review intends to highlight how the integration of emerging “omics” approaches may provide a rational foundation for the comprehensive exploration of molecular pathways and dynamic interactions involved in ALS, for the identification of candidate targets and biomarkers that will assist in the rapid diagnosis and prognosis, lastly for the stratification of patients into different subgroups with the aim of personalized therapeutic strategies. To this purpose, particular emphasis will be placed on some potential therapeutic targets, including neurotrophic factors and histamine signaling that both have emerged as dysregulated at different omics levels in specific subgroups of ALS patients, and have already shown promising results in in vitro and in vivo models of ALS. To conclude, we will discuss about the utility of using integrated omics coupled with network-based approaches to provide additional guidance for personalization of medicine applications in ALS.