Invited Review: Amyotrophic lateral sclerosis represents corticomotoneuronal system failure-Link to article

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The invited review titled "Amyotrophic lateral sclerosis represents corticomotoneuronal system failure" by Andrew Eisen, Steve Vucic, and Matthew C. Kiernan discusses the unique characteristics of amyotrophic lateral sclerosis (ALS) as a specifically human neurodegenerative disease. ALS is linked to the failure of the corticomotoneuronal system, which is a complex network involving the corticomotoneuronal projections primarily found in humans and some dexterous primates. The authors describe how ALS manifests as early loss of skilled motor dexterity and speech, related to the degeneration of large Betz cells in the motor cortex, which have extensive dendritic arborization and are particularly vulnerable to age, environmental stressors, and lifestyle factors. The study delves into the pathogenesis mechanisms, notably the role of the TDP-43 protein, whose nuclear-cytoplasmic shuttling becomes disrupted, leading to toxic aggregates that contribute to neuronal degeneration. ALS is posited as a "dying forward" disease, progressing from the motor cortex down neural pathways, something that current animal models fail to replicate accurately due to the absence of a comparable corticomotoneuronal system.<br /><br />The authors also discuss the potential for precision medicine approaches focusing on the understanding of specific genetic and epigenetic components affecting the corticomotoneuronal system. Challenges in current therapeutic strategies highlight the complexity of ALS. Emerging treatments aim to protect the corticomotoneurons and influence early detection mechanisms which are seen as key to better managing and potentially modifying the disease progression.<br /><br />This review underscores ALS as a distinctively human disorder arising from corticomotoneuronal network failure, suggesting that future therapeutic success will depend on targeted approaches to this unique aspect of human neurophysiology.

Keywords

Amyotrophic lateral sclerosis

ALS

Corticomotoneuronal system

Neurodegenerative disease

Betz cells

TDP-43 protein

Precision medicine

Neuronal degeneration

Genetic components

Therapeutic strategies

amyotrophic lateral sclerosis

ALS