QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 28, 2007, 27(48):13173-13180; doi:10.1523/JNEUROSCI.4057-07.2007

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Gifondorwa, D. J. Articles by Milligan, C. E. Search for Related Content PubMed PubMed Citation Articles by Gifondorwa, D. J. Articles by Milligan, C. E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Amyotrophic Lateral Sclerosis

 Previous Article  |  Next Article 

Neurobiology of Disease
Exogenous Delivery of Heat Shock Protein 70 Increases Lifespan in a Mouse Model of Amyotrophic Lateral Sclerosis

David J. Gifondorwa,^1,3 Mac B. Robinson,¹ Crystal D. Hayes,¹ Anna R. Taylor,⁴ David M. Prevette,¹ Ronald W. Oppenheim,^1,3 James Caress,² and Carolanne E. Milligan^1,3

Departments of ¹Neurobiology and Anatomy, ²Neurology, and ³Program in Neuroscience, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, and ⁴National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892

Correspondence should be addressed to Dr. Carolanne Milligan, Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC 27157. Email: milligan{at}wfubmc.edu

Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disorder that results in the progressive loss of motoneurons (MNs) in the CNS. Several survival and death mechanisms of MNs have been characterized and it has been determined that MNs do not appear to mount a complete stress response, as determined by the lack of heat shock protein 70 (Hsp70) upregulation after several stress paradigms. Hsp70 has been shown to confer neuroprotection and the insufficient availability of Hsp70 may contribute to MNs' susceptibility to death in ALS mice. In this study, recombinant human Hsp70 (rhHsp70) was intraperitoneally injected three times weekly, beginning at postnatal day 50 until endstage, to G93A mutant SOD1 (G93A SOD1) mice. The administration of rhHsp70 was effective at increasing lifespan, delaying symptom onset, preserving motor function and prolonging MN survival. Interestingly, injected rhHsp70 localized to skeletal muscle and was not readily detected in the CNS. Treatment with rhHsp70 also resulted in an increased number of innervated neuromuscular junctions compared with control tissue. Together these results suggest rhHsp70 may delay disease progression in the G93A SOD1 mouse via a yet to be identified peripheral mechanism.

Key words: motoneuron; denervation; NMJ; axonopathy; neurodegeneration; SOD1

---

Received July 5, 2007; revised Oct. 11, 2007; accepted Oct. 16, 2007.

Correspondence should be addressed to Dr. Carolanne Milligan, Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, NC 27157. Email: milligan{at}wfubmc.edu

This article has been cited by other articles:

				C. L. Simpson, R. Lemmens, K. Miskiewicz, W. J. Broom, V. K. Hansen, P. W.J. van Vught, J. E. Landers, P. Sapp, L. Van Den Bosch, J. Knight, et al. Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration Hum. Mol. Genet., February 1, 2009; 18(3): 472 - 481. [Abstract] [Full Text] [PDF]

				M. R. Watson, R. D. Lagow, K. Xu, B. Zhang, and N. M. Bonini A Drosophila Model for Amyotrophic Lateral Sclerosis Reveals Motor Neuron Damage by Human SOD1 J. Biol. Chem., September 5, 2008; 283(36): 24972 - 24981. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help