glial biology in neuromuscular disorders

Neuromuscular disorders are characterized by impaired motor function. The underlying primary defects, however, can be very divers and may arise not only from malfunction of neurons or muscle cells, but also glial cells. The peripheral nerve glia, the Schwann cells, provide axons with an insulating myelin sheath that allows for rapid propagation of electrical impulses. Schwann cells moreover support nerve fibers metabolically and, in the case of terminal Schwann cells, participate in neuromuscular transmission.

So far, more than 1000 mutations in over 80 genes are known to affect Schwann cell or axon function and, hence, cause chronic, progressive deterioration of the peripheral nervous system. These genetically determined neuropathies are collectively referred to as Charcot-Marie-Tooth (CMT) diseases and affect 1 in 2500 humans. Unfortunately, no causal therapy is available for any type of CMT neuropathy, especially because the underlying pathological mechanisms that lead to nerve impairment remain poorly understood. With the help of transgenic techniques in mice, a battery of state of the art behavioral and electrophysiological methods, high resolution microscopy and next generation sequencing approaches, we aim to unravel pathological mechanisms that may help to identify therapeutic targets for this life-burdening diseases.