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dc.contributor.authorRavits, John
dc.contributor.authorAppel, Stanley
dc.contributor.authorBaloh, Robert H.
dc.contributor.authorBarohn, Richard
dc.contributor.authorBrooks, Benjamin Rix
dc.contributor.authorElman, Lauen
dc.contributor.authorFloeter, Mary Kay
dc.contributor.authorMacklis, Jeffrey Daniel
dc.contributor.authorHenderson, Christopher
dc.contributor.authorLomen-Hoerth, Catherine
dc.contributor.authorMccluskey, Leo
dc.contributor.authorMitsumoto, Hiroshi
dc.contributor.authorPrezedborski, Serge
dc.contributor.authorRothstein, Jeffrey
dc.contributor.authorTrojanowski, John
dc.contributor.authorVan Den Berg, Leonard
dc.contributor.authorRingel, Steven
dc.date.accessioned2013-09-13T16:10:43Z
dc.date.issued2013
dc.identifierQuick submit: 2013-08-02T09:54:05-04:00
dc.identifier.citationRavits, John, Stanley Appel, Robert H. Baloh, Richard Barohn, Benjamin Rix Brooks, Lauren Elman, Mary Kay Floeter, et al. 2013. Deciphering amyotrophic lateral sclerosis: what phenotype, neuropathology and genetics are telling us about pathogenesis. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration 14(Suppl 1): 5-18.en_US
dc.identifier.issn2167-8421en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11022234
dc.description.abstractAmyotrophic lateral sclerosis (ALS) is characterized phenotypically by progressive weakness and neuropathologically by loss of motor neurons. Phenotypically, there is marked heterogeneity. Typical ALS has mixed upper motor neuron (UMN) and lower motor neuron (LMN) involvement. Primary lateral sclerosis has predominant UMN involvement. Progressive muscular atrophy has predominant LMN involvement. Bulbar and limb ALS have predominant regional involvement. Frontotemporal dementia has significant cognitive and behavioral involvement. These phenotypes can be so distinctive that they would seem to have differing biology. But they cannot be distinguished, at least neuropathologically or genetically. In sporadic ALS (SALS), they all are characterized by ubiquitinated cytoplasmic inclusions of TDP-43. In familial ALS (FALS), where phenotypes are indistinguishable from SALS and similarly heterogeneous, each mutated gene has its own genetic and molecular signature. Putting this together, since the same phenotypes can have multiple causes including different gene mutations, there must be multiple molecular mechanisms causing ALS and ALS is a syndrome. But since multiple phenotypes can be caused by one single gene mutation, a single molecular mechanism can cause heterogeneity. What the mechanisms are remain unknown, but active propagation of the pathology neuroanatomically seems to be a principle component. Leading candidate mechanisms include RNA processing, cell-cell interactions between neurons and non-neuronal neighbors, focal seeding from a misfolded protein that has prion-like propagation, and fatal errors introduced during neurodevelopment of the motor system. If fundamental mechanisms can be identified and understood, ALS therapy could rationally target progression and stop disease—a goal that seems increasingly achievable.en_US
dc.description.sponsorshipStem Cell and Regenerative Biologyen_US
dc.language.isoen_USen_US
dc.publisherInformaen_US
dc.relation.isversionofdoi:10.3109/21678421.2013.778548en_US
dc.relation.hasversionwww.ncbi.nlm.nih.gov/pubmed/23678876en_US
dash.licenseOAP
dc.subjectALSen_US
dc.subjectPLSen_US
dc.subjectPMAen_US
dc.subjectmotor neuron diseaseen_US
dc.subjectFTDen_US
dc.titleDeciphering Amyotrophic Lateral Sclerosis: What Phenotype, Neuropathology and Genetics Are Telling Us about Pathogenesisen_US
dc.typeJournal Articleen_US
dc.date.updated2013-08-02T13:54:36Z
dc.description.versionAccepted Manuscripten_US
dc.rights.holderRavits J, Appel S, Baloh RH, Barohn R, Brooks BR, Elman L, Floeter MK, Henderson C, Lomen-Hoerth C, Macklis JD, McCluskey L, Mitsumoto H, Przedborski S, Rothstein J, Trojanowski JQ, van den Berg LH, Ringel S
dc.relation.journalAmyotrophic Lateral Sclerosis and Frontotemporal Degenerationen_US
dash.depositing.authorMacklis, Jeffrey Daniel
dc.date.available2013-09-13T16:10:43Z
dc.identifier.doi10.3109/21678421.2013.778548*
dash.authorsorderedfalse
dash.contributor.affiliatedMacklis, Jeffrey


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