Motor neuron diseases (MNDs) comprise a large and heterogeneous group of disorders in which the impairment of neuromuscular unity is the major pathological hallmark, causing severe morbidity to individuals, and frequently leading to death due to respiratory failure. The incidence of MNDs varies in different populations; however, the most prevalent, Amyotrophic Lateral Sclerosis, is estimated to occur globally in around 1/2 per 100 000. As of today, a myriad of pathogenic variants located at more than a hundred genes and loci have been associated with this complex group of entities. Functional studies aiming to understand their physiological impact, both using stem cell and animal models, have greatly increased the knowledge of pathological mechanisms underlying MNDs.
These studies show that common pathways, such as autophagy, protein translation, axon elongation, vesicular trafficking, and RNA metabolism, are particularly affected in these conditions, and could be potential targets for therapeutic interventions. The recent use of antisense oligonucleotides (ASOs), such as spinraza, have successfully decreased the pathological effects of splicing disturbances in Progressive Muscular Atrophy. Despite these findings, similar results for other motor neuron diseases are still pending.
Therefore, research into the molecular underpinnings of disease is still much needed for MNDs. Mechanisms whereby disorders such as ALS manifests in different clinical profiles as different as Frontotemporal dementia or spastic paraplegia are largely unknown and might shed light not only putative treatments but also on central nervous system functioning in adaptative plasticity. Besides, even though a large amount of heritability for MNDs has been already uncovered by whole genome sequencing studies, integrative analyses associating transcriptome and methylome sequencing are still expanding our knowledge on the genetic burden of MNDs in different populations.
In order to address these questions, the editors propose this Research Topic, where review articles, original research, and reports covering recent developments in motor neuron disease research will be published.
The main phenotypes of interest include:
• Amyotrophic Lateral Sclerosis
• Spinobulbar Muscular Atrophy
• Hereditary Spastic Paraplegia
• Primary Lateral Sclerosis
• Progressive Muscular Atrophy
We particularly welcome functional studies and drug-screening assays, both using iPSC-based models and other cellular systems. Human genetics studies in families and cohorts carrying such conditions may also be considered.
Motor neuron diseases (MNDs) comprise a large and heterogeneous group of disorders in which the impairment of neuromuscular unity is the major pathological hallmark, causing severe morbidity to individuals, and frequently leading to death due to respiratory failure. The incidence of MNDs varies in different populations; however, the most prevalent, Amyotrophic Lateral Sclerosis, is estimated to occur globally in around 1/2 per 100 000. As of today, a myriad of pathogenic variants located at more than a hundred genes and loci have been associated with this complex group of entities. Functional studies aiming to understand their physiological impact, both using stem cell and animal models, have greatly increased the knowledge of pathological mechanisms underlying MNDs.
These studies show that common pathways, such as autophagy, protein translation, axon elongation, vesicular trafficking, and RNA metabolism, are particularly affected in these conditions, and could be potential targets for therapeutic interventions. The recent use of antisense oligonucleotides (ASOs), such as spinraza, have successfully decreased the pathological effects of splicing disturbances in Progressive Muscular Atrophy. Despite these findings, similar results for other motor neuron diseases are still pending.
Therefore, research into the molecular underpinnings of disease is still much needed for MNDs. Mechanisms whereby disorders such as ALS manifests in different clinical profiles as different as Frontotemporal dementia or spastic paraplegia are largely unknown and might shed light not only putative treatments but also on central nervous system functioning in adaptative plasticity. Besides, even though a large amount of heritability for MNDs has been already uncovered by whole genome sequencing studies, integrative analyses associating transcriptome and methylome sequencing are still expanding our knowledge on the genetic burden of MNDs in different populations.
In order to address these questions, the editors propose this Research Topic, where review articles, original research, and reports covering recent developments in motor neuron disease research will be published.
The main phenotypes of interest include:
• Amyotrophic Lateral Sclerosis
• Spinobulbar Muscular Atrophy
• Hereditary Spastic Paraplegia
• Primary Lateral Sclerosis
• Progressive Muscular Atrophy
We particularly welcome functional studies and drug-screening assays, both using iPSC-based models and other cellular systems. Human genetics studies in families and cohorts carrying such conditions may also be considered.