Customization of the translational complex regulates mRNA-specific translation to control CNS regeneration.

In the adult mammalian central nervous system (CNS), axons fail to regenerate spontaneously after injury because of a combination of extrinsic and intrinsic factors. Despite recent advances targeting the intrinsic regenerative properties of adult neurons, the molecular mechanisms underlying axon regeneration are not fully understood. Here, we uncover a regulatory mechanism that controls the expression of key proteins involved in regeneration at the translational level. Our results show that mRNA-specific translation is critical for promoting axon regeneration. Indeed, we demonstrate that specific ribosome-interacting proteins, such as the protein Huntingtin (HTT), selectively control the translation of a specific subset of mRNAs. Moreover, modulating the expression of these translationally regulated mRNAs is crucial for promoting axon regeneration. Altogether, our findings highlight that selective translation through the customization of the translational complex is a key mechanism of axon regeneration with major implications in the development of therapeutic strategies for CNS repair.

Exploring the structural and functional stabilities of different paraoxonase-1 formulations through electrophoretic mobilities and enzyme activity parameters under hydrostatic pressure.

Human paraoxonase-1 (HuPON1) is the ideal candidate to engineer as catalytic bioscavenger for pre-treatment and therapy of exposure to toxic organophosphorus compounds. HuPON1 is a naturally-occurring hydrophobic plasma protein associated with a partner, the human phosphate binding protein (HPBP) on high density lipoproteins. The relationships between the composition and the size of multimeric states of HuPON1 are not well understood. Moreover, the effect of HPBP's presence on enzyme catalysis and stability is not clear. The effect of hydrostatic pressure on structural stability and activity of different PON1 preparations (free natural HuPON1 or in the presence of 50% w/w HPBP, hybrid recombinant PON1) was investigated. Results showed that PON1 exists under several multimeric forms, and that the binding of HPBP amends the size of the hetero-oligomeric states and exerts a stabilizing effect on the activities of PON1. Furthermore, high pressure kinetic experiments highlighted the fact that PON1 displays two distinct catalytic behaviors: the first one for arylesterase and lactonase activities and the second one for its organophosphate-hydrolase activity.