Pharmacological manipulation of cell death: clinical applications in sight?

被引:195
作者
Green, DR
Kroemer, G
机构
[1] St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA
[2] Inst Gustave Roussy, CNRS, UMR8125, Villejuif, France
关键词
D O I
10.1172/JCI26321
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
This series of Reviews on cell death explores the creation of new therapies for correcting excessive or deficient death in human disease. Signal transduction pathways controlling cell death and the molecular core machinery responsible for cellular self-destruction have been elucidated with unprecedented celerity during. the last decade, leading to the design of novel strategies for blocking pathological cell loss or for killing unwanted cells. Thus, an increasing number of compounds targeting a diverse range of apoptosis-related molecules are being explored at the preclinical and clinical levels. Beyond the agents that are already FDA approved, a range of molecules targeting apoptosis-regulatory transcription factors, regulators of mitochondrial membrane permeabilization, and inhibitors or activators of cell death-related proteases are under close scrutiny for drug development.
引用
收藏
页码:2610 / 2617
页数:8
相关论文
共 76 条
  • [1] Three-dimensional structure of the apoptosome: Implications for assembly, procaspase-9 binding, and activation
    Acehan, D
    Jiang, XJ
    Morgan, DG
    Heuser, JE
    Wang, XD
    Akey, CW
    [J]. MOLECULAR CELL, 2002, 9 (02) : 423 - 432
  • [2] Bcl-2 family regulation of neuronal development and neurodegeneration
    Akhtar, RS
    Ness, JM
    Roth, KA
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2004, 1644 (2-3): : 189 - 203
  • [3] The survival kinases Akt and Pim as potential pharmacological targets
    Amaravadi, R
    Thompson, CB
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (10) : 2618 - 2624
  • [4] Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death
    Baines, CP
    Kaiser, RA
    Purcell, NH
    Blair, NS
    Osinska, H
    Hambleton, MA
    Brunskill, EW
    Sayen, MR
    Gottlieb, RA
    Dorn, GW
    Robbins, J
    Molkentin, JD
    [J]. NATURE, 2005, 434 (7033) : 658 - 662
  • [5] Structure of Apaf-1 in the auto-inhibited form - A critical role for ADP
    Bao, Q
    Riedl, SJ
    Shi, YG
    [J]. CELL CYCLE, 2005, 4 (08) : 1001 - 1003
  • [6] Properties of the permeability transition pore in mitochondria devoid of cyclophilin D
    Basso, E
    Fante, L
    Fowlkes, J
    Petronilli, V
    Forte, MA
    Bernardi, P
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (19) : 18558 - 18561
  • [7] Death versus survival: functional interaction between the apoptotic and stress-inducible heat shock protein pathways
    Beere, HM
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2005, 115 (10) : 2633 - 2639
  • [8] Lysosomal membrane permeabilization induces cell death in a mitochondrion-dependent fashion
    Boya, P
    Andreau, K
    Poncet, D
    Zamzami, N
    Perfettini, JL
    Metivier, D
    Ojcius, DM
    Jäättelä, M
    Kroemer, G
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (10) : 1323 - 1334
  • [9] Cao GD, 2002, J NEUROSCI, V22, P5423
  • [10] Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function
    Chen, L
    Willis, SN
    Wei, A
    Smith, BJ
    Fletcher, JI
    Hinds, MG
    Colman, PM
    Day, CL
    Adams, JM
    Huang, DCS
    [J]. MOLECULAR CELL, 2005, 17 (03) : 393 - 403