Neuroinflammation as fuel for axonal regeneration: exploring the proteome for underlying molecular players

Neurotrauma and degeneration diminish life quality in our aging society and lead to impairments, mainly because the central nervous system (CNS) of adult mammals lacks the robust capacity to regenerate. Despite intensive research, induction of long-distance axonal regeneration and functional recovery of the damaged CNS remain a challenge. Although neuroinflammation has been put forward as a mechanism to trigger axonal regeneration in the CNS, little is known about the underlying molecules and pathways. Therefore, our overarching goal is to unravel the cellular and molecular players that link inflammation to proper axonal regeneration. Thereto, we will use an inflammatory optic nerve injury model in mice and apply an innovative proteomics approach on retina and optic nerve.

Furthermore, as data obtained in our group indicate matrix metalloproteinase-2 (MMP-2) as a promising regenerative factor that connects ocular inflammation with successful axonal regeneration in the optic nerve, we will further disentangle the pleiotropic role of MMP-2 in axonal outgrowth, elongation and navigation. As such, taking MMP-2 as a lead, we will establish a pipeline for further testing of the selected/identified high-confidence targets, using expression/activity studies and loss/gain-of-function approaches. Overall, the expected outcome of this proposal is the identification and validation of novel benefactors of axonal regeneration that might hold future therapeutic potential.