p75 Neurotrophin Receptor: A Double-Edged Sword in Pathology and Regeneration of the Central Nervous System

The low-affinity nerve growth factor receptor p75(NTR) is a major neurotrophin receptor involved in manifold and pleiotropic functions in the developing and adult central nervous system (CNS). Although known for decades, its entire functions are far from being fully elucidated. Depending on the complex interactions with other receptors and on the cellular context, p75(NTR) is capable of performing contradictory tasks such as mediating cell death as well as cell survival. In parallel, as a prototype marker for certain differentiation stages of Schwann cells and related CNS aldynoglial cells, p75(NTR) has recently gained increasing notice as a marker for cells with proposed regenerative potential in CNS diseases, such as demyelinating disease and traumatic CNS injury. Besides its pivotal role as a marker for transplantation candidate cells, recent studies in canine neuroinflammatory CNS conditions also highlight a spontaneous endogenous occurrence of p75(NTR)-positive glia, which potentially play a role in Schwann cell-mediated CNS remyelination. The aim of the present communication is to review the pleiotropic functions of p75(NTR) in the CNS with a special emphasis on its role as an immunohistochemical marker in neuropathology. Following a brief illustration of the expression of p75(NTR) in neurogenesis and in developed neuronal populations, the implications of p75(NTR) expression in astrocytes, oligodendrocytes, and microglia are addressed. A special focus is put on the role of p75(NTR) as a cell marker for specific differentiation stages of Schwann cells and a regeneration-promoting CNS population, collectively referred to as aldynoglia.