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Article: ATF3 expression improves motor function in the ALS mouse model by promoting motor neuron survival and retaining muscle innervation

TitleATF3 expression improves motor function in the ALS mouse model by promoting motor neuron survival and retaining muscle innervation
Authors
KeywordsActivating Transcription Factor 3/*metabolism
Amyotrophic Lateral Sclerosis/pathology/*physiopathology
Animals
Cell Survival
Disease Models, Animal
Mice
Motor Neurons/*pathology
Muscle, Skeletal/*innervation
Superoxide Dismutase/genetics
Issue Date2014
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings of the National Academy of Sciences, 2014, v. 111 n. 4, p. 1622-1627 How to Cite?
AbstractALS is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons and atrophy of distal axon terminals in muscle, resulting in loss of motor function. Motor end plates denervated by axonal retraction of dying motor neurons are partially reinnervated by remaining viable motor neurons; however, this axonal sprouting is insufficient to compensate for motor neuron loss. Activating transcription factor 3 (ATF3) promotes neuronal survival and axonal growth. Here, we reveal that forced expression of ATF3 in motor neurons of transgenic SOD1G93A ALS mice delays neuromuscular junction denervation by inducing axonal sprouting and enhancing motor neuron viability. Maintenance of neuromuscular junction innervation during the course of the disease in ATF3/SOD1G93A mice is associated with a substantial delay in muscle atrophy and improved motor performance. Although disease onset and mortality are delayed, disease duration is not affected. This study shows that adaptive axonal growth-promoting mechanisms can substantially improve motor function in ALS and importantly, that augmenting viability of the motor neuron soma and maintaining functional neuromuscular junction connections are both essential elements in therapy for motor neuron disease in the SOD1G93A mice. Accordingly, effective protection of optimal motor neuron function requires restitution of multiple dysregulated cellular pathways.
Persistent Identifierhttp://hdl.handle.net/10722/219919
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSeijffers, R-
dc.contributor.authorZhang, J-
dc.contributor.authorMatthews, JC-
dc.contributor.authorChen, A-
dc.contributor.authorTamrazian, E-
dc.contributor.authorBabaniyi, O-
dc.contributor.authorSelig, M-
dc.contributor.authorHynynen, M-
dc.contributor.authorWoolf, CJ-
dc.contributor.authorBrown, RH-
dc.date.accessioned2015-10-02T09:00:02Z-
dc.date.available2015-10-02T09:00:02Z-
dc.date.issued2014-
dc.identifier.citationProceedings of the National Academy of Sciences, 2014, v. 111 n. 4, p. 1622-1627-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/219919-
dc.description.abstractALS is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons and atrophy of distal axon terminals in muscle, resulting in loss of motor function. Motor end plates denervated by axonal retraction of dying motor neurons are partially reinnervated by remaining viable motor neurons; however, this axonal sprouting is insufficient to compensate for motor neuron loss. Activating transcription factor 3 (ATF3) promotes neuronal survival and axonal growth. Here, we reveal that forced expression of ATF3 in motor neurons of transgenic SOD1G93A ALS mice delays neuromuscular junction denervation by inducing axonal sprouting and enhancing motor neuron viability. Maintenance of neuromuscular junction innervation during the course of the disease in ATF3/SOD1G93A mice is associated with a substantial delay in muscle atrophy and improved motor performance. Although disease onset and mortality are delayed, disease duration is not affected. This study shows that adaptive axonal growth-promoting mechanisms can substantially improve motor function in ALS and importantly, that augmenting viability of the motor neuron soma and maintaining functional neuromuscular junction connections are both essential elements in therapy for motor neuron disease in the SOD1G93A mice. Accordingly, effective protection of optimal motor neuron function requires restitution of multiple dysregulated cellular pathways.-
dc.languageeng-
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org-
dc.relation.ispartofProceedings of the National Academy of Sciences-
dc.rightsProceedings of the National Academy of Sciences. Copyright © National Academy of Sciences.-
dc.subjectActivating Transcription Factor 3/*metabolism-
dc.subjectAmyotrophic Lateral Sclerosis/pathology/*physiopathology-
dc.subjectAnimals-
dc.subjectCell Survival-
dc.subjectDisease Models, Animal-
dc.subjectMice-
dc.subjectMotor Neurons/*pathology-
dc.subjectMuscle, Skeletal/*innervation-
dc.subjectSuperoxide Dismutase/genetics-
dc.titleATF3 expression improves motor function in the ALS mouse model by promoting motor neuron survival and retaining muscle innervation-
dc.typeArticle-
dc.identifier.emailZhang, J: jzhang1@hku.hk-
dc.identifier.authorityZhang, J=rp01713-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1314826111-
dc.identifier.pmid24474789-
dc.identifier.pmcidPMC3910594-
dc.identifier.scopuseid_2-s2.0-84893357959-
dc.identifier.volume111-
dc.identifier.issue4-
dc.identifier.spage1622-
dc.identifier.epage1627-
dc.identifier.isiWOS:000330231100087-
dc.publisher.placeUnited States-

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