Administration of Recombinant Heat Shock Protein 70 Delays Peripheral Muscle Denervation in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis
A prominent clinical feature of ALS is muscle weakness due to dysfunction, denervation and degeneration of motoneurons (MNs). While MN degeneration is a late stage event in the ALS mouse model, muscle denervation occurs significantly earlier in the disease. Strategies to prevent this early denervati...
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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/10.1155/2012/170426 |
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| author | David J. Gifondorwa Ramon Jimenz-Moreno Crystal D. Hayes Hesam Rouhani Mac B. Robinson Jane L. Strupe James Caress Carol Milligan |
| author_facet | David J. Gifondorwa Ramon Jimenz-Moreno Crystal D. Hayes Hesam Rouhani Mac B. Robinson Jane L. Strupe James Caress Carol Milligan |
| author_sort | David J. Gifondorwa |
| collection | DOAJ |
| description | A prominent clinical feature of ALS is muscle weakness due to dysfunction, denervation and degeneration of motoneurons (MNs). While MN degeneration is a late stage event in the ALS mouse model, muscle denervation occurs significantly earlier in the disease. Strategies to prevent this early denervation may improve quality of life by maintaining muscle control and slowing disease progression. The precise cause of MN dysfunction and denervation is not known, but several mechanisms have been proposed that involve potentially toxic intra- and extracellular changes. Many cells confront these changes by mounting a stress response that includes increased expression of heat shock protein 70 (Hsp70). MNs do not upregulate Hsp70, and this may result in a potentially increased vulnerability. We previously reported that recombinant human hsp70 (rhHsp70) injections delayed symptom onset and increased lifespan in SOD1G93A mice. The exogenous rhHsp70 was localized to the muscle and not to spinal cord or brain suggesting it modulates peripheral pathophysiology. In the current study, we focused on earlier administration of Hsp70 and its effect on initial muscle denervation. Injections of the protein appeared to arrest denervation with preserved large myelinated peripheral axons, and reduced glial activation. |
| format | Article |
| id | doaj-art-2715d4388d624a5bb555273853e62521 |
| 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-2715d4388d624a5bb555273853e625212025-02-03T06:06:01ZengWileyNeurology Research International2090-18522090-18602012-01-01201210.1155/2012/170426170426Administration of Recombinant Heat Shock Protein 70 Delays Peripheral Muscle Denervation in the SOD1G93A Mouse Model of Amyotrophic Lateral SclerosisDavid J. Gifondorwa0Ramon Jimenz-Moreno1Crystal D. Hayes2Hesam Rouhani3Mac B. Robinson4Jane L. Strupe5James Caress6Carol Milligan7Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USADepartment of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USADepartment of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USADepartment of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USADepartment of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USADepartment of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USAThe ALS Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USADepartment of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USAA prominent clinical feature of ALS is muscle weakness due to dysfunction, denervation and degeneration of motoneurons (MNs). While MN degeneration is a late stage event in the ALS mouse model, muscle denervation occurs significantly earlier in the disease. Strategies to prevent this early denervation may improve quality of life by maintaining muscle control and slowing disease progression. The precise cause of MN dysfunction and denervation is not known, but several mechanisms have been proposed that involve potentially toxic intra- and extracellular changes. Many cells confront these changes by mounting a stress response that includes increased expression of heat shock protein 70 (Hsp70). MNs do not upregulate Hsp70, and this may result in a potentially increased vulnerability. We previously reported that recombinant human hsp70 (rhHsp70) injections delayed symptom onset and increased lifespan in SOD1G93A mice. The exogenous rhHsp70 was localized to the muscle and not to spinal cord or brain suggesting it modulates peripheral pathophysiology. In the current study, we focused on earlier administration of Hsp70 and its effect on initial muscle denervation. Injections of the protein appeared to arrest denervation with preserved large myelinated peripheral axons, and reduced glial activation.http://dx.doi.org/10.1155/2012/170426 |
| spellingShingle | David J. Gifondorwa Ramon Jimenz-Moreno Crystal D. Hayes Hesam Rouhani Mac B. Robinson Jane L. Strupe James Caress Carol Milligan Administration of Recombinant Heat Shock Protein 70 Delays Peripheral Muscle Denervation in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis Neurology Research International |
| title | Administration of Recombinant Heat Shock Protein 70 Delays Peripheral Muscle Denervation in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis |
| title_full | Administration of Recombinant Heat Shock Protein 70 Delays Peripheral Muscle Denervation in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis |
| title_fullStr | Administration of Recombinant Heat Shock Protein 70 Delays Peripheral Muscle Denervation in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis |
| title_full_unstemmed | Administration of Recombinant Heat Shock Protein 70 Delays Peripheral Muscle Denervation in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis |
| title_short | Administration of Recombinant Heat Shock Protein 70 Delays Peripheral Muscle Denervation in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis |
| title_sort | administration of recombinant heat shock protein 70 delays peripheral muscle denervation in the sod1g93a mouse model of amyotrophic lateral sclerosis |
| url | http://dx.doi.org/10.1155/2012/170426 |
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