4F-induced rejuvenation of glia into neural stem cells for brain repair

ended

Although the concept of adult neurogenesis has important implications for regenerative medicine, the formation of new functional neurons from progenitors during adult life is rare and occurs only in confined areas of the mammalian brain . Because adult neurogenesis is limited, the regenerative capacity of the brain is restrained and the possibilities of recovery from damage are almost absent. The WHO* reported that up to 1 billion people, nearly one in six of the world’s population, suffer from neurological disorders. Many of these disorders have the loss or malfunction of neurons in common. Alongside the rapid increase of life expectancy whereby it is estimated that a quarter of Europeans will be over 60 years of age by 2020, these types of disorders are becoming a growing burden for aging societies, in terms of both suffering and economic cost. In Europe, for example, the total cost of brain disorders was estimated at €386 billion in 2004 and increased to €798 billion in 2010. This project, 4F4REJUVENGLIA (short for: 4 factors for rejuvenating glia), focuses on a novel approach to engineer neurogenesis, based on nuclear cell reprogramming technology, to induce regeneration of damaged areas of the brain. The aim is to generate new neurons in regions naturally devoid of neurogenesis. The approach involves the overexpression of the Yamanaka factors directly in parenchymal glia, with the purpose of reprograming/rejuvenating these cells back in development in order to recover their stem cell potential lost during specification (Fig.1). We hypothesise that this “rewinding” to a neural progenitor-like state may rearrange the local environment and remodel it towards a stem cell niche that help instruct and integrate new neurons within the preexisting circuits.