Calpain as a Potential Therapeutic Target in Parkinsons Disease

Author(s): Supriti Samantaray, Swapan K. Ray, Naren L. Banik

Journal Name: CNS & Neurological Disorders - Drug Targets
Formerly Current Drug Targets - CNS & Neurological Disorders

Volume 7 , Issue 3 , 2008

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Pathophysiology of idiopathic Parkinsons disease (PD) is associated with degeneration of dopaminergic neurons and inflammatory responses in the mid-brain substantia nigra (SN). However, central dopaminergic replenishment therapeutic strategy with L-3,4-dihydroxyphenylalanine (L-DOPA), the precursor for dopamine synthesis, does not fully rescue these cells in SN or improve motor function. Besides, prolonged use of L-DOPA worsens the clinical symptoms in PD patients. Thus, there is a possibility that other areas of central nervous system may also be affected in this disease. Spinal cord, the final coordinator of movement in the central nervous system, may be one such site that is critically affected during pathogenesis of this complex movement disorder. In this review, we summarize the evidence in support of involvement of calpain, a Ca2+-activated non-lysosomal protease, in spinal cord degeneration in two models of experimental parkinsonism induced by the neurotoxin 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine and also the environmental toxin rotenone. The key focus of this review is to discuss the role that calpain plays in disrupting the structural and functional integrity of the spinal cord in these experimental models of parkinsonism. A similar disruptive role of calpain has been reported earlier in SN of PD patients as well as in experimental PD animals. Studies in rodent and cell culture models of PD suggest that treatment with calpain inhibitors (e.g., calpeptin, MDL-28170) can prevent neuronal death and restore functions. Furthermore, the degradation of calpain substrates in both brain and spinal cord during pathogenesis of PD suggested a putative role of calpain, and calpain inhibition as a therapeutic strategy in PD.

Keywords: Calpain, experimental parkinsonism, MPTP, Parkinson's disease, rotenone, spinal cord

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Article Details

Year: 2008
Page: [305 - 312]
Pages: 8
DOI: 10.2174/187152708784936680
Price: $65

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PDF: 10