Chapter title |
Sigma-1 Receptor in Motoneuron Disease
|
---|---|
Chapter number | 16 |
Book title |
Sigma Receptors: Their Role in Disease and as Therapeutic Targets
|
Published in |
Advances in experimental medicine and biology, March 2017
|
DOI | 10.1007/978-3-319-50174-1_16 |
Pubmed ID | |
Book ISBNs |
978-3-31-950172-7, 978-3-31-950174-1
|
Authors |
Renzo Mancuso, Xavier Navarro, Mancuso, Renzo, Navarro, Xavier |
Editors |
Sylvia B. Smith, Tsung-Ping Su |
Abstract |
Amyotrophic Lateral Sclerosis (ALS ) is a neurodegenerative disease affecting spinal cord and brain motoneurons , leading to paralysis and early death. Multiple etiopathogenic mechanisms appear to contribute in the development of ALS , including glutamate excitotoxicity, oxidative stress , protein misfolding, mitochondrial defects, impaired axonal transport, inflammation and glial cell alterations. The Sigma-1 receptor is highly expressed in motoneurons of the spinal cord, particularly enriched in the endoplasmic reticulum (ER) at postsynaptic cisternae of cholinergic C-terminals. Several evidences point to participation of Sigma-1R alterations in motoneuron degeneration. Thus, mutations of the transmembrane domain of the Sigma-1R have been described in familial ALS cases. Interestingly, Sigma-1R KO mice display muscle weakness and motoneuron loss. On the other hand, Sigma-1R agonists promote neuroprotection and neurite elongation through activation of protein kinase C on motoneurons in vitro and in vivo after ventral root avulsion. Remarkably, treatment of SOD1 mice, the most usual animal model of ALS , with Sigma-1R agonists resulted in significantly enhanced motoneuron function and preservation, and increased animal survival. Sigma-1R activation also reduced microglial reactivity and increased the glial expression of neurotrophic factors. Two main interconnected mechanisms seem to underlie the effects of Sigma-1R manipulation on motoneurons: modulation of neuronal excitability and regulation of calcium homeostasis. In addition, Sigma-1R also contributes to regulating protein degradation, and reducing oxidative stress. Therefore, the multi-functional nature of the Sigma-1R represents an attractive target for treating aspects of ALS and other motoneuron diseases . |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 31 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 8 | 26% |
Researcher | 5 | 16% |
Student > Ph. D. Student | 5 | 16% |
Student > Bachelor | 3 | 10% |
Other | 1 | 3% |
Other | 3 | 10% |
Unknown | 6 | 19% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 6 | 19% |
Agricultural and Biological Sciences | 4 | 13% |
Medicine and Dentistry | 3 | 10% |
Biochemistry, Genetics and Molecular Biology | 2 | 6% |
Engineering | 2 | 6% |
Other | 5 | 16% |
Unknown | 9 | 29% |