Progress in Therapy Development for Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that cannot be slowed substantially using any currently-available clinical tools. Through decades of studying sporadic and familial ALS (SALS and FALS), researchers are coming to understand ALS as a complex syndrome with...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Neurology Research International |
| Online Access: | http://dx.doi.org/10.1155/2012/187234 |
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| _version_ | 1832560319089606656 |
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| author | Kalina Venkova-Hristova Alexandar Christov Zarine Kamaluddin Peter Kobalka Kenneth Hensley |
| author_facet | Kalina Venkova-Hristova Alexandar Christov Zarine Kamaluddin Peter Kobalka Kenneth Hensley |
| author_sort | Kalina Venkova-Hristova |
| collection | DOAJ |
| description | Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that cannot be slowed substantially using any currently-available clinical tools. Through decades of studying sporadic and familial ALS (SALS and FALS), researchers are coming to understand ALS as a complex syndrome with diverse genetic and environmental etiologies. It is know appreciated that motor neuron degeneration in ALS requires active (gain of function) and passive (loss of function) events to occur in non-neuronal cells, especially astrocytes and microglia. These neuroinflammatory processes produce paracrine factors that detrimentally affect motor neurons, precipitating protein aggregation and compromising cytoskeletal integrity. The result is a loss of neuronal homeostasis and progressive die-back of motor axons culminating in death of the afflicted motor neurons. This review will discuss experimental therapeutics that have been tested in murine ALS models, with an emphasis on those that have progressed to human clinical trials. Reasons will be considered for the frequent failure of preclinical successes to translate into positive clinical outcomes. Finally, this review will explore current trends in experimental therapeutics for ALS with emphasis on the emerging interest in axon guidance signaling pathways as novel targets for pharmacological support of neural cytoskeletal structure and function in order to slow ALS. |
| format | Article |
| id | doaj-art-72eea4146d07405eb86768df0f803b04 |
| institution | Kabale University |
| issn | 2090-1852 2090-1860 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neurology Research International |
| spelling | doaj-art-72eea4146d07405eb86768df0f803b042025-02-03T01:27:50ZengWileyNeurology Research International2090-18522090-18602012-01-01201210.1155/2012/187234187234Progress in Therapy Development for Amyotrophic Lateral SclerosisKalina Venkova-Hristova0Alexandar Christov1Zarine Kamaluddin2Peter Kobalka3Kenneth Hensley4Department of Pathology, University of Toledo Medical Center, 3000 Arlington Avenue, MS1090, Toledo, OH 43614, USADepartment of Pathology, University of Toledo Medical Center, 3000 Arlington Avenue, MS1090, Toledo, OH 43614, USADepartment of Pathology, University of Toledo Medical Center, 3000 Arlington Avenue, MS1090, Toledo, OH 43614, USADepartment of Pathology, University of Toledo Medical Center, 3000 Arlington Avenue, MS1090, Toledo, OH 43614, USADepartment of Pathology, University of Toledo Medical Center, 3000 Arlington Avenue, MS1090, Toledo, OH 43614, USAAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that cannot be slowed substantially using any currently-available clinical tools. Through decades of studying sporadic and familial ALS (SALS and FALS), researchers are coming to understand ALS as a complex syndrome with diverse genetic and environmental etiologies. It is know appreciated that motor neuron degeneration in ALS requires active (gain of function) and passive (loss of function) events to occur in non-neuronal cells, especially astrocytes and microglia. These neuroinflammatory processes produce paracrine factors that detrimentally affect motor neurons, precipitating protein aggregation and compromising cytoskeletal integrity. The result is a loss of neuronal homeostasis and progressive die-back of motor axons culminating in death of the afflicted motor neurons. This review will discuss experimental therapeutics that have been tested in murine ALS models, with an emphasis on those that have progressed to human clinical trials. Reasons will be considered for the frequent failure of preclinical successes to translate into positive clinical outcomes. Finally, this review will explore current trends in experimental therapeutics for ALS with emphasis on the emerging interest in axon guidance signaling pathways as novel targets for pharmacological support of neural cytoskeletal structure and function in order to slow ALS.http://dx.doi.org/10.1155/2012/187234 |
| spellingShingle | Kalina Venkova-Hristova Alexandar Christov Zarine Kamaluddin Peter Kobalka Kenneth Hensley Progress in Therapy Development for Amyotrophic Lateral Sclerosis Neurology Research International |
| title | Progress in Therapy Development for Amyotrophic Lateral Sclerosis |
| title_full | Progress in Therapy Development for Amyotrophic Lateral Sclerosis |
| title_fullStr | Progress in Therapy Development for Amyotrophic Lateral Sclerosis |
| title_full_unstemmed | Progress in Therapy Development for Amyotrophic Lateral Sclerosis |
| title_short | Progress in Therapy Development for Amyotrophic Lateral Sclerosis |
| title_sort | progress in therapy development for amyotrophic lateral sclerosis |
| url | http://dx.doi.org/10.1155/2012/187234 |
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