Caspase-2 and caspase-8 trigger caspase-3 activation following 6-OHDA-induced stress in human dopaminergic neurons differentiated from ReNVM stem cells

Abstract

The study showed that 6OHD-induced toxicity triggered caspase mediated death of dDCN. This finding is in support of previous studies using different PD model showing that 6OHD can induce caspases-2 and -3 activation through apoptotic pathway and that both caspases can activate caspase-3 in PD. In addition, our results suggest that caspase-2 cause's cell death might be via an indirect NF kappaB route. This study has established a PD model which can provide better insight to PD pathogenesis on a biochemical and molecular level, leading to a better understanding of PD and potential for new treatments.

Hyperphosphorylation of CREB in human dopaminergic neurons

“…The cells were maintained in ReNcell NSC maintenance medium [SCM005; Chemicon (Millipore), Watford, UK] and were differentiated into dopaminergic neurons (dDCN), as described previously [12]. To ensure that the dDCN were indeed dopaminergic neurons, the dopamine marker tyrosine hydroxylase was used and the cells were treated with 100 mM 6-OHDA for 2 h to induce stress, please see our recently published article for details [12], after which fresh media were replaced and cells were either collected immediately termed as 0 h, or left in the incubator at 371C and collected after 24 and 72 h. The untreated group was subjected to media change only and was collected at 0 h, termed as control.…”

“…Recently, we and others have shown that ReNVM can be differentiated successfully into DCN (dDCN) and provide a suitable model to study Parkinson's disease pathogenesis [12,13].…”

A 3D human neural cell culture system for modeling Alzheimer's disease

“…We chose the immortalized hNPC cell line ReNcell VM (ReN) as a base for our platform because the cells can be maintained for more than 45 passages, are commercially available, and can differentiate into neurons and glial cells with simple growth-factor deprivation 15–27 . The ReN cells were then transfected with IRES-mediated polycistronic lentiviral vectors containing FAD genes encoding human APP with both K670N/M671L (Swedish) and V717I (London) mutations (APPSL), PSEN1 with ΔE9 mutation (PSEN1(ΔE9)), and APPSL/PSEN1(ΔE9) with GFP or mCherry as a reporter for viral infection (Fig.…”

Melanocortin-1 receptor activation is neuroprotective in mouse models of neuroinflammatory disease

“…Therefore, human neurons were differentiated from the ReNcell VM progenitor cell line (38) and treated with glutamate in the absence or presence of NDP-MSH. Similar to murine cells, human neurons expressed MC1R and up-regulated NR4A1 on mRNA and protein level in response to NDP-MSH (Fig.…”