Tremor in the Age of Omics: An Overview of the Transcriptomic Landscape of Essential Tremor.

Essential Tremor (ET) is the most common movement disorder and has a worldwide prevalence of 1%, including 5% of the population over 65 years old. It is characterized by an active, postural or kinetic tremor, primarily affecting the upper limbs, and is diagnosed based on clinical characteristics. The pathological mechanisms of ET, however, are mostly unknown. Moreover, despite its high heritability, genetic studies of ET genetics have yielded mixed results. Transcriptomics is a field that has the potential to reveal valuable insights about the processes and pathogenesis of ET thus providing an avenue for the development of more effective therapies. With the emergence of techniques such as single-cell and single-nucleus RNA sequencing (scRNA-seq and snRNA-seq), molecular and cellular events can now be more closely examined, providing valuable insights into potential causal mechanisms. In this review, we review the growing literature on transcriptomic studies in ET, aiming to identify biological pathways involved and explore possible avenues for further ET research. We emphasized the convergence on shared of biological pathways across several studies, specifically axonal guidance and calcium signaling. These findings posit multiple hypotheses linking both pathways through the regulation of axonal and synaptic plasticity. We conclude that increasing the sample size is vital to uncover the subtleties of ET clinical and pathological heterogeneity. Additionally, integrating Multiomics approaches should provide a comprehensive understanding of the disease's pathophysiology.