Extranigral neurodegeneration in Parkinson's disease.
It is widely known that the pathophysiology of idiopathic Parkinson's disease (PD) is associated with neurodegeneration and inflammatory responses in the midbrain substantia nigra. However, the possibility of neurodegeneration and inflammatory responses in other areas of the central nervous system (CNS) in course of the pathogenesis of PD remains to be explored. In this investigation, we provide evidence in support of the hypothesis that spinal cord, the final coordinator of movement, is also involved during parkinsonian degeneration using two distinct experimental parkinsonism models induced by the neurotoxin 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) and the environmental toxin rotenone. A key focus of our study is the role that calpain, a Ca(2+)-activated neutral protease, plays in disrupting the structural-functional integrity of the spinal cord in the context of spinal cord degeneration in experimental parkinsonism. We examined the mechanisms of calpain-mediated neuronal death in differentiated spinal cord motoneuron cultures following exposure to the active parkinsonian toxins 1-methyl-4-phenyl-pyridinium ion (MPP(+)) and rotenone and also tested the neuroprotective efficacy of calpeptin, a calpain inhibitor, in these cell culture models of experimental parkinsonism. Our results implied that spinal cord motoneurons could be a potential extranigral target of neurodegeneration during pathogenesis of PD in the CNS and that calpain inhibition could provide neuroprotection.
Samantaray
Supriti
S
Division of Neurology, Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina, USA.
Butler
Jonathan T
JT
Ray
Swapan K
SK
Banik
Naren L
NL
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002154:Calpain / Q000378:metabolism*; D002460:Cell Line; D004151:Dipeptides / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000473:pathology* / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology; D010300:Parkinson Disease / Q000473:pathology* / Q000503:physiopathology; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology; D012402:Rotenone / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013378:Substantia Nigra / Q000473:pathology*; D014475:Uncoupling Agents / Q000494:pharmacology
D004151:Dipeptides; D018696:Neuroprotective Agents; D009498:Neurotoxins; D014475:Uncoupling Agents; D012402:Rotenone; C071482:calpeptin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D002154:Calpain