title: Death receptor Fas (CD95) signaling in the central nervous system: tuning neuroplasticity?
abstract: 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.
authors.affiliation: Department of Neurodegeneration and Restorative Research, Center for Molecular Physiology of the Brain, University of Göttingen, D-37073 Göttingen, Germany.
authors.forename: Arno
authors.initials: A
authors.lastname: Reich
authors.forename: Christopher
authors.initials: C
authors.lastname: Spering
authors.forename: Jörg B
authors.initials: JB
authors.lastname: Schulz
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D002490:Central Nervous System / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D053222:Fas Ligand Protein