Dysregulation of the Autophagy-Endolysosomal System in Amyotrophic Lateral Sclerosis and Related Motor Neuron Diseases
Amyotrophic lateral sclerosis (ALS) is a heterogeneous group of incurable motor neuron diseases (MNDs) characterized by a selective loss of upper and lower motor neurons in the brain and spinal cord. Most cases of ALS are sporadic, while approximately 5–10% cases are familial. More than 16 causative...
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Wiley
2012-01-01
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| Series: | Neurology Research International |
| Online Access: | http://dx.doi.org/10.1155/2012/498428 |
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| author | Asako Otomo Lei Pan Shinji Hadano |
| author_facet | Asako Otomo Lei Pan Shinji Hadano |
| author_sort | Asako Otomo |
| collection | DOAJ |
| description | Amyotrophic lateral sclerosis (ALS) is a heterogeneous group of incurable motor neuron diseases (MNDs) characterized by a selective loss of upper and lower motor neurons in the brain and spinal cord. Most cases of ALS are sporadic, while approximately 5–10% cases are familial. More than 16 causative genes for ALS/MNDs have been identified and their underlying pathogenesis, including oxidative stress, endoplasmic reticulum stress, excitotoxicity, mitochondrial dysfunction, neural inflammation, protein misfolding and accumulation, dysfunctional intracellular trafficking, abnormal RNA processing, and noncell-autonomous damage, has begun to emerge. It is currently believed that a complex interplay of multiple toxicity pathways is implicated in disease onset and progression. Among such mechanisms, ones that are associated with disturbances of protein homeostasis, the ubiquitin-proteasome system and autophagy, have recently been highlighted. Although it remains to be determined whether disease-associated protein aggregates have a toxic or protective role in the pathogenesis, the formation of them results from the imbalance between generation and degradation of misfolded proteins within neuronal cells. In this paper, we focus on the autophagy-lysosomal and endocytic degradation systems and implication of their dysfunction to the pathogenesis of ALS/MNDs. The autophagy-endolysosomal pathway could be a major target for the development of therapeutic agents for ALS/MNDs. |
| format | Article |
| id | doaj-art-04df581e45944eb9bc3c4e62c2bd968f |
| institution | Kabale University |
| issn | 2090-1852 2090-1860 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
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| series | Neurology Research International |
| spelling | doaj-art-04df581e45944eb9bc3c4e62c2bd968f2025-02-03T01:32:51ZengWileyNeurology Research International2090-18522090-18602012-01-01201210.1155/2012/498428498428Dysregulation of the Autophagy-Endolysosomal System in Amyotrophic Lateral Sclerosis and Related Motor Neuron DiseasesAsako Otomo0Lei Pan1Shinji Hadano2Department of Molecular Life Sciences, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, JapanDepartment of Molecular Life Sciences, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, JapanDepartment of Molecular Life Sciences, Tokai University School of Medicine, 143 Shimokasuya, Isehara 259-1193, JapanAmyotrophic lateral sclerosis (ALS) is a heterogeneous group of incurable motor neuron diseases (MNDs) characterized by a selective loss of upper and lower motor neurons in the brain and spinal cord. Most cases of ALS are sporadic, while approximately 5–10% cases are familial. More than 16 causative genes for ALS/MNDs have been identified and their underlying pathogenesis, including oxidative stress, endoplasmic reticulum stress, excitotoxicity, mitochondrial dysfunction, neural inflammation, protein misfolding and accumulation, dysfunctional intracellular trafficking, abnormal RNA processing, and noncell-autonomous damage, has begun to emerge. It is currently believed that a complex interplay of multiple toxicity pathways is implicated in disease onset and progression. Among such mechanisms, ones that are associated with disturbances of protein homeostasis, the ubiquitin-proteasome system and autophagy, have recently been highlighted. Although it remains to be determined whether disease-associated protein aggregates have a toxic or protective role in the pathogenesis, the formation of them results from the imbalance between generation and degradation of misfolded proteins within neuronal cells. In this paper, we focus on the autophagy-lysosomal and endocytic degradation systems and implication of their dysfunction to the pathogenesis of ALS/MNDs. The autophagy-endolysosomal pathway could be a major target for the development of therapeutic agents for ALS/MNDs.http://dx.doi.org/10.1155/2012/498428 |
| spellingShingle | Asako Otomo Lei Pan Shinji Hadano Dysregulation of the Autophagy-Endolysosomal System in Amyotrophic Lateral Sclerosis and Related Motor Neuron Diseases Neurology Research International |
| title | Dysregulation of the Autophagy-Endolysosomal System in Amyotrophic Lateral Sclerosis and Related Motor Neuron Diseases |
| title_full | Dysregulation of the Autophagy-Endolysosomal System in Amyotrophic Lateral Sclerosis and Related Motor Neuron Diseases |
| title_fullStr | Dysregulation of the Autophagy-Endolysosomal System in Amyotrophic Lateral Sclerosis and Related Motor Neuron Diseases |
| title_full_unstemmed | Dysregulation of the Autophagy-Endolysosomal System in Amyotrophic Lateral Sclerosis and Related Motor Neuron Diseases |
| title_short | Dysregulation of the Autophagy-Endolysosomal System in Amyotrophic Lateral Sclerosis and Related Motor Neuron Diseases |
| title_sort | dysregulation of the autophagy endolysosomal system in amyotrophic lateral sclerosis and related motor neuron diseases |
| url | http://dx.doi.org/10.1155/2012/498428 |
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