Molecular targets for pharmacological cytoprotection

A. Balla, Balázs Tóth, György Timár, Judit Bak, Peter Krajcsi

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Cell death is common to many pathological conditions. In the past two decades, research into the mechanism of cell death has characterized the cardinal features of apoptosis and necrosis, the two distinct forms of cell death. Studies using in vivo disease models have provided evidence that apoptosis is induced by an array of pathological stimuli. Thus, molecular components of the machinery of apoptosis are potential pharmacological targets. The mechanism of apoptosis can be dissected into: (i) the initiation and signaling phase, (ii) the signal amplification phase, and (iii) the execution phase. Reflecting on the diversity of apoptotic stimuli, the initiation and signaling phase utilizes a variety of molecules: free radicals, ions, plasma membrane receptors, members of the signaling kinase cascades, transcription factors, and signaling caspases. In most of the apoptotic scenarios, impairment of mitochondrial function is an early event. Dysfunctioning mitochondria release more free radicals and hydrolytic enzymes (proteases and nucleases), amplifying the primary death signal. In the final phase of apoptosis, executioner caspases are activated. Substrates of the executioner caspases include nucleases, members of the cellular repair apparatus, and cytoskeletal proteins. Partial proteolysis of these substrates leads to distinctive morphological and biochemical changes, the hallmarks of apoptosis. The first steps toward pharmacological utilization of specific modifiers of apoptosis have been promising. However, since the potential molecular targets of cytoprotective therapy play important roles in the maintenance of cellular homeostasis, specificity (diseased versus healthy tissue) of pharmacological modulation is the key to success.

Original languageEnglish
Pages (from-to)769-777
Number of pages9
JournalBiochemical Pharmacology
Volume61
Issue number7
DOIs
Publication statusPublished - Apr 1 2001

Fingerprint

Cytoprotection
Pharmacology
Apoptosis
Cell death
Caspases
Cell Death
Free Radicals
Play Therapy
Proteolysis
Mitochondria
Cytoskeletal Proteins
Substrates
Cell membranes
Machinery
Amplification
Homeostasis
Repair
Peptide Hydrolases
Transcription Factors
Necrosis

Keywords

  • Apoptosis
  • Caspase
  • Cytoprotection
  • NF-κB
  • NOS
  • PARP

ASJC Scopus subject areas

  • Pharmacology

Cite this

Molecular targets for pharmacological cytoprotection. / Balla, A.; Tóth, Balázs; Timár, György; Bak, Judit; Krajcsi, Peter.

In: Biochemical Pharmacology, Vol. 61, No. 7, 01.04.2001, p. 769-777.

Research output: Contribution to journalArticle

Balla, A. ; Tóth, Balázs ; Timár, György ; Bak, Judit ; Krajcsi, Peter. / Molecular targets for pharmacological cytoprotection. In: Biochemical Pharmacology. 2001 ; Vol. 61, No. 7. pp. 769-777.
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