Relaño-Ginés Aroa, Lehmann Sylvain, Crozet Carole
Institut de Génétique Humaine; CNRS-UPR 1142; Montpellier, France.
Institut de Génétique Humaine; CNRS-UPR 1142; Montpellier, France; IRMB; INSERM-UM1 U1040; Pathophysiology, Diagnosis and Cell Therapy of Neurodegenerative Disorders; CHU de Montpellier; Montpellier, France.
Prion. 2014;8(3):240-6. doi: 10.4161/pri.29021. Epub 2014 May 15.
Scientific advances in stem cell biology and adult neurogenesis have raised the hope that neurodegenerative disorders could benefit from stem cell-based therapy. Adult neurogenesis might be part of the physiological regenerative process, however it might become impaired by the disease's mechanism and therefore contribute to neurodegeneration. In prion disorders this endogenous repair system has rarely been studied. Whether adult neurogenesis plays a role or not in brain repair or in the propagation of prion pathology remains unclear. We have recently investigated the status of adult neural stem cells isolated from prion-infected mice. We were able to show that neural stem cells accumulate and replicate prions thus resulting in an alteration of their neuronal destiny. We also reproduced these results in adult neural stem cells, which were infected in vitro. The fact that endogenous adult neurogenesis could be altered by the accumulation of misfolded prion protein represents another great challenge. Inhibiting prion propagation in these cells would thus help the endogenous neurogenesis to compensate for the injured neuronal system. Moreover, understanding the endogenous modulation of the neurogenesis system would help develop effective neural stem cell-based therapies.
干细胞生物学和成年神经发生领域的科学进展带来了一种希望，即神经退行性疾病可能会受益于基于干细胞的疗法。成年神经发生可能是生理再生过程的一部分，然而它可能会因疾病机制而受损，从而导致神经退行性变。在朊病毒疾病中，这种内源性修复系统很少被研究。成年神经发生在脑修复或朊病毒病理传播中是否起作用仍不清楚。我们最近研究了从朊病毒感染小鼠中分离出的成年神经干细胞的状态。我们能够证明神经干细胞会积累并复制朊病毒，从而导致其神经元命运发生改变。我们也在体外感染的成年神经干细胞中重现了这些结果。错误折叠的朊病毒蛋白的积累可能改变内源性成年神经发生这一事实代表了另一个巨大挑战。因此，抑制这些细胞中的朊病毒传播将有助于内源性神经发生补偿受损的神经元系统。此外，了解神经发生系统的内源性调节将有助于开发有效的基于神经干细胞的疗法。
