Selective loss of nuclear permeability has been associated with virus-mediated and caspase-dependent cell death. In apoptosis, processing of several components of the envelope is downstream of caspase activation and thereby downstream of the mitochondrial signals for caspase activation. Disassembly of the nuclear envelope, intranuclear proteins and chromosomal DNA are likely to play an important role in promoting disposal of the nucleus and its content. Probably because nuclear permeabilization is thought to be a late event in death programmes, only a handful of studies have examined functional and structural alterations of Nuclear Pore Complex (NPC) during neuronal injury and death. We study the redistribution of proteins across the nuclear envelope during excitotoxicity in rodent neurons and in C.elegans deg-3 mutant. Through a combination of fluorescent confocal imaging and biochemical studies, we have ordered the events that promote alterations in nucleocytoplasmic transport and loss of nucleoporins. We unveil a new mechanism that shows changes in NPC function and we propose that the signalling between the nucleus and the rest of the cell may have a relevant function in the early phases as well as in the execution of caspase-independent cell death.