Fas ligand/Fas system in the brain: regulator of immune and apoptotic responses

Brain Res Brain Res Rev. 2004 Jan;44(1):65-81. doi: 10.1016/j.brainresrev.2003.08.007.


Apoptosis, also known as programmed cell death, is the major type of cell death involved in normal development, regeneration, proliferation and pathologic degeneration in the central nervous system (CNS). The apoptotic process can be divided further into two pathways depending on the involvement of mitochondria and related biochemical cascades. The internal pathway of apoptosis is initiated by a variety of cytotoxic stimuli and mediated by the release of cytochrome c and subsequent activation of downstream caspases. The external pathway is mainly triggered by ligation of death receptors such as Fas, tumor necrosis factor (TNF)-related apoptosis inducing ligand-R1 (TRAIL-R1), TRAIL-R2 and TNFRp55, and mediated by direct activation of upstream caspases. The Fas-FasL system has been known as a prototypic inducer of extrinsic cell death responsible for cell-mediated cytotoxicity, peripheral immune regulation, immune privilege and "counterattack" of malignant tumor cells against the host immune system. Fas and FasL are expressed in the normal CNS, and expression increases in inflamed and degenerated brains. Like other specialized tissues such as the eye and testis, the Fas-FasL system is thought to be involved in immune suppressed status in the CNS. Expression of Fas and FasL is significantly elevated in a variety of the neurologic disorders, suggesting the possibility that this system may play roles in degenerative and inflammatory responses in the CNS. Therefore, the FasL-Fas system should be considered as a double-edged sword in the CNS: maintaining the immune suppressed status in normal brain and inducing neuronal cell death and inflammation in a variety of neurologic disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Apoptosis / physiology
  • Brain / immunology*
  • Brain / metabolism
  • Brain / pathology
  • Brain Diseases / immunology
  • Brain Diseases / metabolism
  • Brain Diseases / pathology
  • Fas Ligand Protein
  • Humans
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism


  • FASLG protein, human
  • Fas Ligand Protein
  • Membrane Glycoproteins