The Role of TNF Related Apoptosis-Inducing Ligand in Neurodegenerative Diseases

A hallmark of all forms of neurodegenerative diseases is impairment of neuronal functions,and in many casesneuronal cell death.Although the etiology of neurodegenerative diseases may be distinct,different diseases displaya similar pathogenesis,for example abnormal immunity within the central nervous system(CNS),activation ofmacrophage/microglia and the involvement of proinflammatory cytokines.Recent studies show that neurons in aneurodegenerative state undergo a highly regulated programmed cell death,also called apoptosis.TNF-relatedapoptosis-inducing ligand(TRAIL),a member of the TNF family,has been shown to be involved in apoptosisduring many diseases.As one member of a death ligand family,TRAIL was originally thought to target only tumorcells and was not present in CNS.However,recent data showed that TRAIL was unregulated in HIV-1-infected andimmune-activated macrophages,a major disease inducing cell during HIV-1-assoeiated dementia(HAD).TRAIL isalso induced on neuron by β-amyloid protein,an important pathogen for Alzheimer’s disease.In this review,wesummarize the possible common aspects that TRAIL involved those neurodegenerative diseases,TRAIL inducedapoptosis signaling in the CNS cells,and specific role of TRAIL in individual diseases.Cellular & MolecularImmunology.2005;2(2):113-122.