Implications of altered apoptosis in diabetes mellitus and autoimmune disease

Citation
T. Hayashi et Dl. Faustman, Implications of altered apoptosis in diabetes mellitus and autoimmune disease, APOPTOSIS, 6(1-2), 2001, pp. 31-45
Citations number
122
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Cell & Developmental Biology
Journal title
APOPTOSIS
ISSN journal
1360-8185 → ACNP
Volume
6
Issue
1-2
Year of publication
2001
Pages
31 - 45
Database
ISI
SICI code
1360-8185(200102)6:1-2<31:IOAAID>2.0.ZU;2-G
Abstract
Lymphocyte development, selection and education represent tightly controlle d immune processes that normally prevent autoimmunity. Lymphocyte developme nt requires cellular selection through apoptosis to remove potentially auto reactive cells. Dysregulated apoptosis, both interrupted as well as accetua ted apoptosis, are now demonstrated as central defects in diverse human and murine autoimmune disease. In murine models of autoimmune lupus, mutations in cell death receptor CD95 (Fas) and its ligand CD95L (FasL) have been id entified; these errors create a lymphoid system resistant to apoptosis. In contract, select lymphoid subpopulations of auto immune diabetic mice have accelerated apoptosis due to faulty activation of transcription factor NF-k appaB that normally protects against apoptotic death. The genetic basis of interrupted NF-kappaB in diabetes is a gene defect in an essential subunit of the proteasome. Although no specific gene in most common forms of human autoimmune disease has been identified, functional assays repeatedly demons trate apoptotic defects in multiple cellular signaling pathways for cell de ath.