Neuroprotection in the peripheral nervous system: Rationale for more effective therapies

Most peripheral neuropathies are length dependent and result in distal axonal degeneration rather than loss of neuronal cell bodies. Available therapies for axonal peripheral neuropathies are designed to control painful symptoms and not to treat the underlying axonal degeneration. Many neuroprotective therapies are being developed, primarily for central nervous system disorders such as stroke or multiple sclerosis. However, strategies with the purpose of promoting survival of injured neurons (ie, preventing cell death) may not be applicable in many peripheral nervous system illnesses when the primary pathologic disorder that leads to symptoms is distal axonal degeneration. Neuronal cell death, if it occurs, is often a late event and may be untreatable in the near future. In contrast, distal axonal degeneration is an early event that may be amenable to treatment. Mechanistic studies that examine the axonglia interaction and axonal biology are likely to yield novel therapeutic targets for peripheral neuropathies.