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Abstract Details

PAK2 Is Necessary for Myelination in the Peripheral Nerve System
Neuromuscular and Clinical Neurophysiology (EMG)
S21 - Inherited Myopathies and Neuropathies: New Therapeutic Approaches and Observations (2:36 PM-2:48 PM)
009
Myelination enables electrical impulses to propagate on axons at the highest speed, encoding essential life functions. The Rho family GTPases, RAC1 and CDC42, have been shown to critically regulate Schwann cell myelination. PAK2 is an effector of RAC1/CDC42, but its specific role in myelination remains undetermined. 
To investigate P21-activated kinase 2 (PAK2) function in the peripheral nerve system.
We produced a Schwann cell-specific knockout mouse of Pak2 (scPak2−/−) to evaluate PAK2’s role in myelination.

Deletion of Pak2 specifically in mouse Schwann cells resulted in severe hypomyelination, slowed nerve conduction velocity, and behavior dysfunctions in the scPak2−/− peripheral nerve. Many Schwann cells in scPak2−/−sciatic nerves were arrested at the stage of axonal sorting. These abnormalities were rescued by reintroducing Pak2, but not the kinase-dead mutation of Pak2, via lentivirus delivery to scPak2−/− Schwann cells in vivo. Moreover, ablation of Pak2 in Schwann cells blocked the promyelinating effect driven by neuregulin-1, prion protein, and inactivated RAC1/CDC42. Conversely, the ablation of Pak2 in neurons exhibited no phenotype. Such PAK2 activity can also be either enhanced or inhibited by different myelin lipids.

We have identified a novel promyelinating factor, PAK2, that acts as a critical convergence point for multiple promyelinating signaling pathways. The promyelination by PAK2 is Schwann cell-autonomous. Myelin lipids, identified as inhibitors or activators of PAK2, may be utilized to develop therapies for repairing abnormal myelin in peripheral neuropathies.

Authors/Disclosures
Jun Li (Harris Methodist Hospital)
PRESENTER
The institution of Dr. Li has received personal compensation in the range of $500-$4,999 for serving as a Consultant for FDA. The institution of Dr. Li has received research support from NIH. Dr. Li has a non-compensated relationship as a Associate Editor of ACTN journal with ANA that is relevant to AAN interests or activities.
Bo Hu (Houston Methodist Hospital) Dr. Hu has nothing to disclose.
Daniel Moiseev Daniel Moiseev has nothing to disclose.
No disclosure on file
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