Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterised by the death of upper and lower motor neurons (MN) and severe muscle atrophy. In recent years, it has been shown that the degeneration MNs can also be caused or exacerbated by other neighbouring cells such as glial cells or skeletal muscle, and these are also known as non-cell autonomous mechanisms. Regarding skeletal muscle, muscle atrophy is not a mere result of denervation, but ALS patients and animal models show intrinsic muscle defects independently of MN degeneration. Likewise, synapses between motor nerve terminals and skeletal muscle fibres occur at the neuromuscular junction (NMJ). Defects in NMJs prior to MN degeneration or symptom onset have also been widely reported in ALS, leading to the proposal of the ‘dying-back’ theory, which postulates that MN defects begin at the distal nerve terminals located in the NMJ, and are transmitted retrogradely to the MN soma, ultimately inducing its death.
- Which postulates that MN defects begin at the distal nerve terminals located in the NMJ, and are transmitted retrogradely to the MN soma, ultimately inducing its death.
- Hypothesis has been addressed by focusing on the contribution of different cell types, thus allowing a more comprehensive view of the NMJ environment.
- Finally, it has been shown that muscle signalling is also altered in ALS, which could negatively affect NMJ formation and, consequently.
- Contribute to the pathogenesis of the disease. These findings place the skeletal muscle as a possible target for future therapeutic strategies, opening new possibilities for the treatment of the disease through therapeutic approaches aimi.
In this PhD Thesis we have studied the pathological events underlying the neuromuscular junction dismantlement in the early stages of ALS disease, which may provoke a retrograde stress resulting in the dismantling of the NMJ and the subsequent dying-back phenomenon. This hypothesis has been addressed by focusing on the contribution of different cell types, thus allowing a more comprehensive view of the NMJ environment. Finally, it has been shown that muscle signalling is also altered in ALS,.
- Which postulates that MN defects begin at the distal nerve terminals located in the NMJ, and are transmitted retrogradely to the MN soma, ultimately inducing its death.
- Hypothesis has been addressed by focusing on the contribution of different cell types, thus allowing a more comprehensive view of the NMJ environment.
- Finally, it has been shown that muscle signalling is also altered in ALS, which could negatively affect NMJ formation and, consequently.
- Contribute to the pathogenesis of the disease. These findings place the skeletal muscle as a possible target for future therapeutic strategies, opening new possibilities for the treatment of the disease through therapeutic approaches aimi.
hich could negatively affect NMJ formation and, consequently, contribute to the pathogenesis of the disease. These findings place the skeletal muscle as a possible target for future therapeutic strategies, opening new possibilities for the treatment of the disease through therapeutic approaches aiming to restore or modulate its function at the NMJ level.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterised by the death of upper and lower motor neurons (MN) and severe muscle atrophy. In recent years, it has been shown that the degeneration MNs can also be caused or exacerbated by other neighbouring cells such as glial cells or skeletal muscle, and these are also known as non-cell autonomous mechanisms. Regarding skeletal muscle, muscle atrophy is not a mere result of denervation, but ALS patients and animal models show intrinsic muscle defects independently of MN degeneration. Likewise, synapses between motor nerve terminals and skeletal muscle fibres occur at the neuromuscular junction (NMJ). Defects in NMJs prior to MN degeneration or symptom onset have also been widely reported in ALS, leading to the proposal of the ‘dying-back’ theory, which postulates that MN defects begin at the distal nerve terminals located in the NMJ, and are transmitted retrogradely to the MN soma, ultimately inducing its death. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterised by the death of upper and lower motor neurons (MN) and severe muscle atrophy. In recent years,
it has been shown that the degeneration MNs can also be caused or exacerbated by other neighbouring cells such as glial cells or skeletal muscle, and these are also known as non-cell autonomous mechanisms. Regarding skeletal muscle, muscle atrophy is not a mere result of denervation, but ALS patients and animal models show intrinsic muscle defects independently of MN degeneration. Likewise, synapses between motor nerve terminals and skeletal muscle fibres occur at the neuromuscular junction (NMJ). Defects in NMJs prior to MN degeneration or symptom onset have also been widely reported in ALS, leading to the proposal of the ‘dying-back’ theory, which postulates that MN defects begin at the distal nerve terminals located in the NMJ, and are transmitted retrogradely to the MN soma, ultimately inducing its death.