Calpains are calcium-dependent proteases activated in apoptotic cell death and neurodegeneration. Dorsal root ganglion (DRG) sensory neurons are among the cellular types most affected in Friedreich Ataxia. The authors have previously demonstrated that frataxin-deficient DRGs show calpain activation, alteration in calcium levels and decreased content of the Na+/Ca2+ exchanger (NCLX). This transporter is involved in mitochondrial calcium efflux. In this study, a time-course analysis of several parameters altered in a frataxin-deficient DRGs is performed. These include decline of NCLX levels, calcium accumulation, mitochondrial depolarization, α-fodrin fragmentation and apoptotic cell death. Furthermore, the effect of the calpain inhibitors MDL28170 and Calpeptin on these parameters were analysed. These inhibitors increase NCLX levels, protect sensory neurons from neurite degeneration and calcium accumulation, and restore mitochondrial membrane potential. In addition, calpain 1 reduction alleviated neurodegeneration in frataxin-deficient DRG neurons. These results strengthen the hypothesis of a central role for calcium homeostasis and calpains in frataxin-deficient dorsal root ganglia neurons.

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