The mitochondria permeability transition pore complex in the brain with interacting proteins - promising targets for protection in neurodegenerative diseases

被引:47
作者
Azarashvili, Tamara [1 ,2 ]
Stricker, Rolf [1 ]
Reiser, Georg [1 ]
机构
[1] Otto VonGuericke Univ Magdegurg, Inst Neurobiochim, Fak Med, D-39120 Magdeburg, Germany
[2] Russian Acad Sci, Inst Theoret & Expt Biophys, Moscow 142290, Russia
关键词
apoptosis; 2; 3 '-cyclic nucleotide 3 '-phosphodiesterase (CNP); neuroprotection; p42(IP4) (centaurin alpha 1; ADAP; 1); protein phosphorylation; translocator protein (TSPO); PERIPHERAL BENZODIAZEPINE-RECEPTOR; 2'; 3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE; APOPTOSIS-INDUCING FACTOR; DIAZEPAM-BINDING INHIBITOR; NEURONAL CELL-DEATH; 18-KDA TRANSLOCATOR PROTEIN; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; RAT-BRAIN; ADP/ATP CARRIER;
D O I
10.1515/BC.2010.070
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mitochondria increasingly attract attention as control points within the mechanisms of neuronal death. Mitochondria play a central role in swinging the balance in favor of either survival or death of brain tissue. Cell death in vertebrates proceeds mostly via the mitochondrial pathway of apoptosis. Permeability transition pore (PTP) development in mitochondria is a decisive stage of apoptosis. Therefore, regulation of the permeability of both outer and inner mitochondria] membranes helps to induce neuroprotection. Through PTP control, mitochondria can to a large degree manage the intracellular calcium homeostasis, and thus control the potent death cascade initiated by excess calcium. Here we summarize the evidence for the role of mitochondria in brain cell death. We describe the involvement of the 18-kDa translocator protein (TSPO; previously called peripheral benzodiazepine receptor), and of two new mitochondrial proteins, that is, 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) and p42(IP4) (also designated centaurin alpha 1; ADAP 1), in the control of the PTP. Furthermore, ligands of TSPO, as well as substrates of CNP., are possible modulators of PTP function. This scenario of control and regulation of PTP function might provide multiple important targets, which are suitable for developing protective strategies for neurons and non-neuronal brain cells in therapies of neurodegenerative diseases.
引用
收藏
页码:619 / 629
页数:11
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