Peripheral neuropathies: molecular mechanisms and the treatment

The goal of the study is to elucidate the molecular mechanisms responsible for the development of peripheral neuropathies and to revert them to alleviate the symptoms of peripheral neuropathies.

Peripheral neuropathies are the disorders caused by injuries to the peripheral nerves, which connect the brain and the spinal cord to the peripheral organs. More than 70% of the peripheral neuropathies are sensory neuropathies. Some peripheral neuropathies are inherited (e.g. Charcot Marie Tooth (CMT) disease), but others are acquired (e.g. chemotherapy induced peripheral neuropathy (CIPN), Guillain-Barré Syndrome (GBS), and diabetic neuropathy).

In the peripheral nerves, the axon and the supporting Schwann cells are in close proximity with each other. Some of axons are wrapped by lipid-rich myelin, which is formed by the plasma membrane of Schwann cells. The myelin sheath is a non-continuous structure and is periodically separated by non-myelinated intervals of axon, called nodes of Ranvier. Each nodal region is comprised of several domains including node, two flanking paranodes and two flanking juxta-paranodes. Each domain consists of a highly specific set of proteins including ion channels, transmembrane proteins, and cell adhesion molecules. Any disruption of this molecular organization leads to various neurodegenerative disorders and thus axon-glia interaction is a sensitive indicator of axon integrity and health.

The focus of this research is to study the changes in the molecular composition of node of Ranvier during various peripheral neuropathies. Further studies will be directed towards the protection and preservation of such molecular architecture at the node of Ranvier to preserve the axon-glia interactions and ameliorate the peripheral neuropathies.