The Ubiquitin Proteasome System in Neuromuscular Disorders : Moving Beyond Movement
(2020) In International Journal of Molecular Sciences 21(17).- Abstract
Neuromuscular disorders (NMDs) affect 1 in 3000 people worldwide. There are more than 150 different types of NMDs, where the common feature is the loss of muscle strength. These disorders are classified according to their neuroanatomical location, as motor neuron diseases, peripheral nerve diseases, neuromuscular junction diseases, and muscle diseases. Over the years, numerous studies have pointed to protein homeostasis as a crucial factor in the development of these fatal diseases. The ubiquitin-proteasome system (UPS) plays a fundamental role in maintaining protein homeostasis, being involved in protein degradation, among other cellular functions. Through a cascade of enzymatic reactions, proteins are ubiquitinated, tagged, and... (More)
Neuromuscular disorders (NMDs) affect 1 in 3000 people worldwide. There are more than 150 different types of NMDs, where the common feature is the loss of muscle strength. These disorders are classified according to their neuroanatomical location, as motor neuron diseases, peripheral nerve diseases, neuromuscular junction diseases, and muscle diseases. Over the years, numerous studies have pointed to protein homeostasis as a crucial factor in the development of these fatal diseases. The ubiquitin-proteasome system (UPS) plays a fundamental role in maintaining protein homeostasis, being involved in protein degradation, among other cellular functions. Through a cascade of enzymatic reactions, proteins are ubiquitinated, tagged, and translocated to the proteasome to be degraded. Within the ubiquitin system, we can find three main groups of enzymes: E1 (ubiquitin-activating enzymes), E2 (ubiquitin-conjugating enzymes), and E3 (ubiquitin-protein ligases). Only the ubiquitinated proteins with specific chain linkages (such as K48) will be degraded by the UPS. In this review, we describe the relevance of this system in NMDs, summarizing the UPS proteins that have been involved in pathological conditions and neuromuscular disorders, such as Spinal Muscular Atrophy (SMA), Charcot-Marie-Tooth disease (CMT), or Duchenne Muscular Dystrophy (DMD), among others. A better knowledge of the processes involved in the maintenance of proteostasis may pave the way for future progress in neuromuscular disorder studies and treatments.
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- author
- Bachiller, Sara LU ; Alonso-Bellido, Isabel M. ; Real, Luis Miguel ; Pérez-Villegas, Eva María ; Venero, José Luis ; Deierborg, Tomas LU ; Armengol, José Ángel and Ruiz, Rocío
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- neuromuscular disorder, neuromuscular junction, proteasome, synapse, ubiquitin, UPS
- in
- International Journal of Molecular Sciences
- volume
- 21
- issue
- 17
- article number
- 6429
- publisher
- MDPI AG
- external identifiers
-
- scopus:85090727729
- pmid:32899400
- ISSN
- 1422-0067
- DOI
- 10.3390/ijms21176429
- language
- English
- LU publication?
- yes
- id
- d6be6f4d-4adc-4bd2-9b1d-a59c60bba994
- date added to LUP
- 2020-09-29 15:22:43
- date last changed
- 2024-10-17 10:42:34
@article{d6be6f4d-4adc-4bd2-9b1d-a59c60bba994, abstract = {{<p>Neuromuscular disorders (NMDs) affect 1 in 3000 people worldwide. There are more than 150 different types of NMDs, where the common feature is the loss of muscle strength. These disorders are classified according to their neuroanatomical location, as motor neuron diseases, peripheral nerve diseases, neuromuscular junction diseases, and muscle diseases. Over the years, numerous studies have pointed to protein homeostasis as a crucial factor in the development of these fatal diseases. The ubiquitin-proteasome system (UPS) plays a fundamental role in maintaining protein homeostasis, being involved in protein degradation, among other cellular functions. Through a cascade of enzymatic reactions, proteins are ubiquitinated, tagged, and translocated to the proteasome to be degraded. Within the ubiquitin system, we can find three main groups of enzymes: E1 (ubiquitin-activating enzymes), E2 (ubiquitin-conjugating enzymes), and E3 (ubiquitin-protein ligases). Only the ubiquitinated proteins with specific chain linkages (such as K48) will be degraded by the UPS. In this review, we describe the relevance of this system in NMDs, summarizing the UPS proteins that have been involved in pathological conditions and neuromuscular disorders, such as Spinal Muscular Atrophy (SMA), Charcot-Marie-Tooth disease (CMT), or Duchenne Muscular Dystrophy (DMD), among others. A better knowledge of the processes involved in the maintenance of proteostasis may pave the way for future progress in neuromuscular disorder studies and treatments.</p>}}, author = {{Bachiller, Sara and Alonso-Bellido, Isabel M. and Real, Luis Miguel and Pérez-Villegas, Eva María and Venero, José Luis and Deierborg, Tomas and Armengol, José Ángel and Ruiz, Rocío}}, issn = {{1422-0067}}, keywords = {{neuromuscular disorder; neuromuscular junction; proteasome; synapse; ubiquitin; UPS}}, language = {{eng}}, number = {{17}}, publisher = {{MDPI AG}}, series = {{International Journal of Molecular Sciences}}, title = {{The Ubiquitin Proteasome System in Neuromuscular Disorders : Moving Beyond Movement}}, url = {{http://dx.doi.org/10.3390/ijms21176429}}, doi = {{10.3390/ijms21176429}}, volume = {{21}}, year = {{2020}}, }