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Thus, to understand the comprehensive pathophysiology underlying this devastating disease, postmortem spinal cord tissue samples (cervical, thoracic, and lumbar segments) from patients with <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> were analyzed compared to age\u2010matched normal subjects or Alzheimer's disease for selective molecular markers of neurodegeneration and inflammation. Distal axonal degeneration, relative abundance of both sensory and motor neuron death, selective loss of Ch<jats:styled-content style=\"fixed-case\">AT<\/jats:styled-content><jats:sup>+<\/jats:sup> motoneurons, reactive astrogliosis, microgliosis, increased cycloxygenase\u20102 (Cox\u20102) expression, and infiltration of T cells were observed in spinal cord of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> patients compared to normal subjects. Biochemical analyses of spinal cord tissues revealed associated inflammatory and proteolytic events (elevated levels of Cox\u20102, expression and activity of \u03bc\u2010 and m\u2010calpain, degradation of axonal neurofilament protein, and concomitantly low levels of endogenous inhibitor \u2013 calpastatin) in spinal cord of <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> patients. Thus, pathologically upregulated calpain activity in spinal cords of patients with <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> may contribute to inflammatory response\u2010mediated neuronal death, leading to motor dysfunction.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12374-fig-0005-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>We proposed calpain over\u2010activation and calpain\u2010calpastatin dysregulation driving in a cascade of inflammatory responses (microglial activation and T cell infiltration) and degenerative pathways culminating in axonal degeneration and neuronal death in spinal cord of Parkinson's disease patients. This may be one of the crucial mechanisms in the degenerative process.<\/jats:p>","DOI":"10.1111\/jnc.12374","type":"journal-article","created":{"date-parts":[[2013,7,22]],"date-time":"2013-07-22T11:38:21Z","timestamp":1374493101000},"page":"880-890","source":"Crossref","is-referenced-by-count":37,"title":["Critical role of calpain in spinal cord degeneration in <scp>P<\/scp>arkinson's disease"],"prefix":"10.1111","volume":"127","author":[{"given":"Supriti","family":"Samantaray","sequence":"first","affiliation":[{"name":"Department of Neurosciences Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varduhi H.","family":"Knaryan","sequence":"additional","affiliation":[{"name":"Department of Neurosciences Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald C.","family":"Shields","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The George Washington University Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naren L.","family":"Banik","sequence":"additional","affiliation":[{"name":"Department of Neurosciences Medical University of South Carolina Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,8,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00964996"},{"key":"e_1_2_8_3_1","first-page":"1","article-title":"Neuroanatomy and pathology of sporadic Parkinson's disease","volume":"201","author":"Braak H.","year":"2009","journal-title":"Adv. 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