Biology subjects

Nawabi, H.

Publications and source records attributed to Nawabi, H..

3 recordsLinked to original sources

bioRxiv2022

The RSK-RPS6 axis controls the preconditioning effect and induces spinal cord regeneration

Unlike immature neurons and neurons from the peripheral nervous system (PNS), mature neurons from the central nervous system (CNS) cannot regenerate after injury. In the past 15 years, huge progress has been made to identify molecules and pathways necessary for neuroprotection and/or regeneration after CNS injury. In most regenerative models, phosphorylated ribosomal protein S6 (p-RPS6) is upregulated in neurons, which is often associated with an activation of the mTOR pathway. However, the exact contribution of post-translational modifications of this ribosomal protein in CNS regeneration remains elusive. In this study, we demonstrate that RPS6 phosphorylation is essential for PNS and CNS regeneration. We show that this phosphorylation is induced during the preconditioning effect in dorsal root ganglion (DRG) neurons, and that it is controlled by the p90S6 kinase RSK2. Our results reveal that RSK2 controls the preconditioning effect and that the RSK2-RPS6 axis is key for this process, as well as for PNS regeneration. Finally, we demonstrate that RSK2 promotes CNS regeneration in the dorsal column and allows functional recovery. Our data establish the critical role of RPS6 phosphorylation controlled by RSK2 in CNS regeneration and give new insights into the mechanism related to axon growth and circuit formation after traumatic lesion.

neuroscience↗

bioRxiv2021

Axon guidance modalities in CNS regeneration revealed by quantitative proteomic analysis

Long-distance regeneration of the central nervous system (CNS) has been achieved from the eye to the brain through activation of neuronal molecular pathways or pharmacological approaches. Unexpectedly, most of the regenerative fibers display guidance defects, which prevents reinnervation and further functional recovery. Therefore, characterizing the mature neuronal environment is essential to understand the adult axonal guidance in order to complete the circuit reconstruction. To this end, we used mass spectrometry to characterize the proteomes of major nuclei of the adult visual system: suprachiasmatic nucleus (SCN), ventral and dorsal lateral geniculate nucleus (vLGN, dLGN) and superior colliculus (SCol)), as well as the optic chiasm. These analyses revealed the presence of guidance molecules and guidance-associated factors in the adult visual targets. Moreover, by performing bilateral optic nerve crush, we showed that the expression of some proteins was significantly modulated by the injury in the visual targets, even in the ones most distal to the lesion site. On another hand, we found that the expression of guidance molecules was not modified upon injury. This implies that these molecules may possibly interfere with the reinnervation of the brain targets. Together, our results provides an extensive characterization of the molecular environment in intact and injured conditions. These findings open new ways to correct regenerating axon guidance notably by manipulating the expression of the corresponding guidance receptors in the nervous system.

neuroscience↗

bioRxiv2020

Adult mouse retina explants: an ex vivo window to explore central nervous system diseases

When the developing central nervous system (CNS) becomes mature, it loses its ability to regenerate. Therefore, any insult to adult CNS leads to a permanent and irreversible loss of motor and cognitive functions. For a long time, much effort has been deployed to uncover mechanisms of axon regeneration in the CNS. It is now well understood that neurons themselves lose axon regeneration capabilities during development, and also after a lesion or in pathological conditions. Since then, many molecular pathways such as mTOR and JAK/STAT have been associated with axon regeneration. However, no functional recovery has been achieved yet. Today, there is a need not only to identify new molecules implicated in adult CNS axon regeneration, but also to decipher the fine molecular mechanisms associated with regeneration failure. This is critical to make progress in our understanding of neuroprotection and neuroregeneration and for the development of new therapeutic strategies. In this context, it remains particularly challenging to address molecular mechanisms in in vivo models of CNS regeneration. The extensive use of embryonic neurons as in vitro model is a source of bias, as they have the intrinsic competence to grow their axon upon injury, unlike mature neurons. In addition, this type of dissociated neuronal cultures lack a tissue environment to recapitulate properly molecular and cellular events in vitro. Here, we propose to use cultures of adult retina explants to fill this gap. The visual system - which includes the retina and optic nerve - is a gold-standard model to study axon regeneration and degeneration in the mature CNS. Cultures of adult retina explants combine two advantages: they have the simplicity of embryonic neurons cultures and they recapitulate all the aspects of in vivo features in the tissue. Importantly, it is the most appropriate tool to date to isolate molecular and cellular events of axon regeneration and degeneration of the adult CNS in a dish. This ex vivo system allows to set up a large range of experiments to decipher the fine molecular and cellular regulations underlying mature CNS axon growth.

neuroscience↗