Death Receptor Fas (CD95) Signaling in the Central Nervous System: Tuning Neuroplasticity?

Trends Neurosci. 2008 Sep;31(9):478-86. doi: 10.1016/j.tins.2008.06.007. Epub 2008 Aug 3.


For over a decade, neuroscientific research has focused on processes of apoptosis and its contribution to the pathophysiology of neurological diseases. In the central nervous system, the degree of intrinsic mitochondrial-mediated apoptotic signaling expresses a cell's individual metabolic stress, whereas activation of the extrinsic death receptor-induced cascade is regarded as a sign of imbalanced cellular networks. Under physiological conditions, most neurons possess death receptors without being sensitive to receptor-mediated apoptosis. This paradox raises two questions: what is the evolutionary advantage of expressing potentially harmful proteins? How is their signaling controlled? This review summarizes the functional relevance of FasL-Fas signaling--a quintessential death ligand/receptor system--in different neurological disease models ranging from traumatic, inflammatory and ischemic to neurodegenerative processes. Furthermore, it outlines alternative non-apoptotic Fas signaling, shedding new light on its neuroplastic capacity. Finally, receptor-proximal regulatory proteins are introduced and identified as potential protagonists of disease-modifying neurological therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • Apoptosis / physiology*
  • Central Nervous System / metabolism*
  • Fas Ligand Protein / metabolism
  • Humans
  • Neuronal Plasticity / physiology*
  • Signal Transduction / physiology*


  • Antigens, CD
  • Fas Ligand Protein