There are different kind of ALS diseases. ALS is not well defined, there are no quick tests or biomarkers. And once it is diagnosed (usually 2 years after the o

There are different kind of ALS diseases. ALS is not well defined, there are no quick tests or biomarkers. And once it is diagnosed (usually 2 years after the onset) the patient lives only two years (but that can vary much). From a practical point of view there are roughly 50% of patients (pALS) that carry a mutation on SOD1 gene and most of the rest have TDP-43 bodies inclusions in their neuron's cytoplasm. Abnormal TDP-43 is also seen in other CNS diseases such as Alzheimer. This article tells that abnormal TDP-43 stems from ADAR2 downregulation and Calpain abnormal activity. ADAR protein is a RNA-binding protein, which functions in RNA-editing through post-transcriptional modification of mRNA transcripts by changing the nucleotide content of the RNA. So affected motor neurons bearing TDP-43 pathology invariably exhibit failure in RNA editing at the GluA2 glutamine/arginine (Q/R) site due to down-regulation of adenosine deaminase acting on RNA 2 (ADAR2). The authors tell that exaggerated Ca2+ influx through the abnormal AMPA receptors overactivates calpain, a Ca2+-dependent protease, that cleaves TDP-43 into aggregation-prone fragments, which serve as seeds for TDP-43 pathology. I believe this publication is novel and important in the ALS field, any comment?