Abstract
Neuro-muscular disorders include a variety of diseases induced by genetic mutations resulting in muscle weakness and waste, swallowing and breathing difficulties. However, muscle alterations and nerve depletions involve specific molecular and cellular mechanisms which lead to the loss of motor-nerve or skeletal-muscle function, often due to an excessive cell death. Morphological and molecular studies demonstrated that a high number of these disorders seem characterized by an upregulated apoptosis which significantly contributes to the pathology. Cell death involvement is the consequence of some cellular processes that occur during diseases, including mitochondrial dysfunction, protein aggregation, free radical generation, excitotoxicity and inflammation. The latter represents an important mediator of disease progression, which, in the central nervous system, is known as neuroinflammation, characterized by reactive microglia and astroglia, as well the infiltration of peripheral monocytes and lymphocytes. Some of the mechanisms underlying inflammation have been linked to reactive oxygen species accumulation, which trigger mitochondrial genomic and respiratory chain instability, autophagy impairment and finally neuron or muscle cell death. This review discusses the main inflammatory pathways contributing to cell death in neuro-muscular disorders by highlighting the main mechanisms, the knowledge of which appears essential in developing therapeutic strategies to prevent the consequent neuron loss and muscle wasting.
Highlights
Injury or dysfunctions of the motor neuron, the pheripheral nerve or muscles are correlated to a group of disorders known as neuro-muscular diseases [1,2,3,4], which include motoneuron disorders, diseases of the pheripheral nerve or of neuromuscular junction, and muscle disease such as muscular dystrophies [5,6,7] and myopathies
Alterations in mitochondrial morphology and dynamics observed in the pathogenesis of amyotrophic lateral sclerosis (ALS) seem due to high levels of free radicals and oxidative stress, as well as to the modification of the amount of proteins involved in mitochondrial fusion and fission
There is a recognized multitude of neuro-muscular disorders, this review describes the role of inflammation in motor neuron disorders by highlighting the involvement of the main pathways which lead to neuron death
Summary
Injury or dysfunctions of the motor neuron, the pheripheral nerve or muscles are correlated to a group of disorders known as neuro-muscular diseases [1,2,3,4], which include motoneuron disorders, diseases of the pheripheral nerve or of neuromuscular junction, and muscle disease such as muscular dystrophies [5,6,7] and myopathies (see Table 1 in which two main diseases for each class have been reported). This review is an update of the role of inflammation in inducing cell death in neuro-muscular disorders by highlighting the main inflammatory pathways and discussing their relationship with the innate immune system. The review focuses on the crucial role of inflammation correlated to cell death by deepening these. Biomolecules 2021, 11, 1109 aspects of motor neuron diseases. In these pathologies, a motor unit number reduction has been documented [10,11], even if the molecular mediators which lead to inflammation and neuron cell death have been poorly characterized. Two prominent motor neuron diseases, amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), have been discussed as highlighting the relationship between inflammation and neuron death
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