RNA Toxicity Mechanisms and Therapeutic Development in Neurological and Neuromuscular Disorders, Volume II

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Background

Microsatellite expansion diseases are caused by the expansion of short nucleotide repeats in the coding or non-coding regions of the impaired genes, resulting in neurodegenerative and neuromuscular disorders. Among them, we can mention Fragile-X syndrome, Fragile X-associated tremor/ataxia syndrome (FXTAS), Friedreich ataxia, Frontotemporal Dementia/Amyotrophic Lateral Sclerosis, Huntington's disease, Myotonic dystrophy (DM) and Spinocerebellar ataxias (SCAs).

The recent and rapid advances in the mechanistic studies have revealed several novel pathogenic mechanisms involved in these disorders: loss of the impaired gene’s function, gain of functions caused by toxic polypeptides, non-coding RNA or dipeptide repeats due to repeat-associated non-AUG translation.

This scientific progress has led to the development of potential therapeutic strategies for individual diseases. In fact, despite each of these diseases is characterized by a unique pathogenic mechanism underlying the microsatellite expansion, some common molecular and clinical features are present and shared between these disorders, such as accumulation of RAN proteins, dysregulation of RNA processing, aberrant nucleocytoplasmic transport and tauopathy.

Therefore, a better understanding of the causal mechanism leading to the neurological features observed in patients affected by these diseases would certainly provide valuable information for the development of therapeutic approaches.

In the first edition of this Research Topic, the focus has been on the involvement of dysregulated RNA metabolism in the diseased contexts, and on the establishment of models and tools for the study of disease pathogenesis and therapeutic development.

In this second volume, in addition to the advancement in understanding the contribution of dysregulated RNA metabolism to the molecular and clinical features, we aim to accumulate knowledge on the biophysical and structural biology area in order to deepen our understanding of the RNA-mediated pathogenesis.

Structural insights about toxic RNA will especially enable us to perform a rational drug design on RNAs as targets.

In this Research Topic, we encourage the submission of review articles, that will help consolidate the recent findings, as well as original research articles highlighting the latest advances in the pathogenesis and development of therapeutic strategies.

Keywords: RNA toxicity, Neuromuscular disorders, RNA-mediated pathogenesis, Neurological Disorders, Therapeutic strategies

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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