Ninglu Gao

1 Introduction Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease [1-3]. The etiology of ALS remains largely unclear; however, interactions between genetic and environmental factors are likely to underpin disease susceptibility [4]. ALS is likely derived from cortical influences that appear to involve a multistep process, with a long presymptomatic period [3-8].

Introduction/Aims Amyotrophic lateral sclerosis (ALS) lacks reliable biomarkers to predict disease trajectories or guide therapeutic strategies. Sirtuin 2 (SIRT2), a NAD+-dependent deacetylase implicated in cytoskeletal destabilization and neuroinflammatory pathways in preclinical ALS models, represents a promising yet unvalidated biomarker candidate. We aimed to translate preclinical findings by validating SIRT2's role in ALS.