Neuropathology and omics in motor neuron diseases

Motor neuron diseases, including amyotrophic lateral sclerosis (ALS), are devastating disorders and effective therapies have not yet been established. One of the reasons for this lack of therapeutics, especially in sporadic ALS (SALS), is attributed to the absence of excellent disease models reflecting its pathology. For this purpose, identifying important key molecules for ALS pathomechanisms and developing disease models is crucial, and omics approaches, including genomics, transcriptomics and proteomics, have been employed. In particular, transcriptome analysis using cDNA microarray is the most popular omics approach and we have previously identified dynactin‐1 as an important molecule downregulated in the motor neurons of SALS patients from the early stage of the disease. Dynactin‐1 is also known as a causative gene in familial ALS (FALS). Dynactin‐1 is a major component of the dynein/dynactin motor protein complex functioning in retrograde axonal transport. In motor neuron diseases as well as other neurodegenerative diseases, the role of axonal transport dysfunction in their pathogenesis always draws attention, but its precise mechanisms remain to be fully elucidated. In this article, we review our previous omics approach to SALS and the role of dynactin‐1 in the pathogenesis of ALS. Finally, we emphasize the need for creating novel SALS disease models based on the results of omics analysis, especially based on the observation that dynactin‐1 gene expression was downregulated in SALS motor neurons.