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Brain : a Journal of Neurology Nov 2023Amyotrophic lateral sclerosis (ALS), the major adult-onset motor neuron disease, has been viewed almost exclusively as a disease of upper and lower motor neurons, with... (Review)
Review
Amyotrophic lateral sclerosis (ALS), the major adult-onset motor neuron disease, has been viewed almost exclusively as a disease of upper and lower motor neurons, with muscle changes interpreted as a consequence of the progressive loss of motor neurons and neuromuscular junctions. This has led to the prevailing view that the involvement of muscle in ALS is only secondary to motor neuron loss. Skeletal muscle and motor neurons reciprocally influence their respective development and constitute a single functional unit. In ALS, multiple studies indicate that skeletal muscle dysfunction might contribute to progressive muscle weakness, as well as to the final demise of neuromuscular junctions and motor neurons. Furthermore, skeletal muscle has been shown to participate in disease pathogenesis of several monogenic diseases closely related to ALS. Here, we move the narrative towards a better appreciation of muscle as a contributor of disease in ALS. We review the various potential roles of skeletal muscle cells in ALS, from passive bystanders to active players in ALS pathophysiology. We also compare ALS to other motor neuron diseases and draw perspectives for future research and treatment.
Topics: Adult; Humans; Amyotrophic Lateral Sclerosis; Motor Neurons; Muscle, Skeletal; Neuromuscular Junction; Muscle Weakness
PubMed: 37327376
DOI: 10.1093/brain/awad202 -
Annual Review of Pathology Jan 2024Tauopathies are a diverse group of progressive and fatal neurodegenerative diseases characterized by aberrant tau inclusions in the central nervous system. Tau protein... (Review)
Review
Tauopathies are a diverse group of progressive and fatal neurodegenerative diseases characterized by aberrant tau inclusions in the central nervous system. Tau protein forms pathologic fibrillar aggregates that are typically closely associated with neuronal cell death, leading to varied clinical phenotypes including dementia, movement disorders, and motor neuron disease. In this review, we describe the clinicopathologic features of tauopathies and highlight recent advances in understanding the mechanisms that lead to spread of pathologic aggregates through interconnected neuronal pathways. The cell-to-cell propagation of tauopathy is then linked to posttranslational modifications, tau fibril structural variants, and the breakdown of cellular protein quality control.
Topics: Humans; Neurodegenerative Diseases; Brain; Tauopathies; Neurons
PubMed: 37832941
DOI: 10.1146/annurev-pathmechdis-051222-120750