Mike Fainzilber, Weizmann Institute of Science, Dept. of Biological Chemistry, Revohot, Israel

Importin-Mediated Activation of Intrinsic Regeneration Mechanisms

Funded in: 2013, 2014, 2015

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Problem: Regeneration of the axons of central neurons is poor

Target: Transmission of retrograde injury signals to the cell body and into the cell nucleus

Goal: Using retrograde transportation for new strategies for neural repair


There is a significant difference between the regeneration capacity of a peripheral nerve lesion and the lesion of the axon of a central neuron. Lesion of the peripheral nerve induces a regenerative response in the cell body activating an intrinsic gene expression program that allows for robust axonal re-growth.  In contrast the regeneration of axons of central neurons is very poor as adult CNS neurons lose their axon growth ability.

Following a lesion injury signals are released locally at the axon’s lesion site. In the peripheral nervous system (PNS) the response of the cell to axonal injury is dependent on the transport of these injury signals from lesion site to the cell body and the nucleus. A family of proteins called Importins plays a crucial role in the transmission of such retrograde injury signals to the cell body and into the cell nucleus followed by an activation of the regeneration program. There are some observations that suggest that one of the reasons for differential intrinsic regeneration capacity of central neurons versus peripheral neurons might be a deficit in retrograde injury signaling caused by lack of importin β1 in central axons. This project we will examine this hypothesis.

Determining the mechanisms underlying the intrinsic limitation of an effective injury signaling in a central tract has the potential to suggest new strategies for neural repair and may contribute in future to the development of clinical approaches to enhance neuronal growth capacity after injury.