Cell regeneration in the CNS

How do cells tick? Discovering this secret is currently one of the principal challenges not only for cancer specialists but also for spinal cord researchers. The better one has investigated signal chains and metabolic processes in neurons, the greater are the chances of influencing cell biology and being able to activate healing processes.

One of these studies which raises new hopes of cell regeneration in the central nervous system was published in “Neuron”, the leading science magazine for neurosciences. Researchers at the Universities of Harvard (Boston, USA) and Carleton (Ottawa, CAN) demonstrated in an animal experiment, with financial support from the Wings for Life Foundation, the mode of regeneration of adult neurons via manipulation of growth factors.
The basic problem confronted by the scientists is the following: adult cells of the central nervous system lose their ability to grow. This especially concerns axons - long, fibre-like projections of neurons which are responsible for passing on electrical impulses in the nervous system.

In studies conducted thus far, "blocking" growth factors were identified in the central nervous system. The group of scientists at the Universities of Harvard and Carleton working with Prof. Dr. Zhigang He finally discovered, a year ago, that the elimination of two proteins (PTEN and TSC1) causes "brake pads"  to be swept out of the way. Thus, the scientists were able to achieve what they call robust regeneration of adult neurons. These investigations were also sponsored and funded by Wings for Life.

In the most recently published scientific paper, Zhigang He and his team focused on identifying additional factors that play a key role in the re-initiated regeneration process.
The researchers concentrated on a very specific cytokine (cytokines are defined as glycoproteins that regulate growth and exact differentiation in cells). The scientists isolated SOCS3  (Suppressor oft Cytokine Signaling 3) which blocks specific activities in cells, and eliminated it. Their mouse experiment was successful: the regeneration process of neurons in the eyes was markedly stimulated by this measure. The process was further augmented by direct injection of a different cytokine (CNTF, Ciliary Neurotrophic Factor) into the eye.
These highly complex processes in the cells may be summarised as follows: The results of studies conducted thus far suggest that one of the reasons for the failure of natural regeneration of adult neurons is that, due to injury, the produced growth factors are not sufficient to adequately re-initiate the regeneration process. In fact, some growth factors even paralyse this process.

The scientists are now pinning their hopes on the development of further strategies to gain full control of those regulators in the neurons that act as brakes. The importance thereof has been confirmed by the moderately successful regeneration achieved thus far by the use of cytokines which are simply administered from the outside without interfering with the operational mechanisms of individual cells.

Original article: SOCS3 deletion promotes optic nerve regeneration in vivo. Smith PD, Sun F, Park KK, Cai B, Wang C, Kuwako K, Martinez-Carrasco I, Connolly L, He Z. Neuron. 2009 Dec 10;64(5):617-23.