Apoptotic and antiapoptotic mechanisms in stroke

Mark P. Mattson, Carsten Culmsee, Fang Yu Zai

Research output: Contribution to journalArticle

Abstract

Apoptosis is a form of programmed cell death that occurs in neurons during development of the nervous system and may also be a prominent form of neuronal death in chronic neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. Recent findings also implicate apoptosis in neuronal degeneration after ischemic brain injury in animal models of stroke. Activation of both apoptotic and antiapoptotic signaling cascades occurs in neurons in animal and cell culture models of stroke. Apoptotic cascades involve: increased levels of intracellular oxyradicals and calcium; induction of expression of proteins such as Par-4 (prostate apoptosis response-4), which act by promoting mitochondrial dysfunction and suppressing antiapoptotic mechanisms; mitochondrial membrane depolarization, calcium uptake, and release of factors (e.g., cytochrome c) that ultimately induce nuclear DNA condensation and fragmentation; activation of cysteine proteases of the caspase family; activation of transcription factors such as AP-1 that may induce expression of ″killer genes.″ Antiapoptotic signaling pathways are activated by neurotrophic factors, certain cytokines, and increases in oxidative and metabolic stress. Such protective pathways include: activation of the transcription factors (e.g., nuclear factor-κB, NF-κB) that induce expression of stress proteins, antioxidant enzymes, and calcium-regulating proteins; phosphorylation-mediated modulation of ion channels and membrane transporters; cytoskeletal alterations that modulate calcium homeostasis; and modulation of proteins that stabilize mitochondrial function (e.g., Bcl-2). Intervention studies in experimental stroke models have identified a battery of approaches of potential benefit in reducing neuronal death in stroke patients, including administration of antioxidants, calcium-stabilizing agents, caspase inhibitors, and agents that activate NF-κB. Interestingly, recent studies suggest novel dietary approaches (e.g., food restriction and supplementation with antioxidants) that may reduce brain damage following stroke.

Original languageEnglish (US)
Pages (from-to)173-187
Number of pages15
JournalCell and Tissue Research
Volume301
Issue number1
StatePublished - 2000
Externally publishedYes

Fingerprint

Stroke
Calcium
Chemical activation
Antioxidants
Apoptosis
Neurons
Brain
Animals
Transcription Factors
Modulation
Physiological Stress
Phosphorylation
Caspase Inhibitors
Membrane Transport Proteins
Cysteine Proteases
Excipients
Mitochondrial Proteins
Transcription Factor AP-1
Depolarization
Nerve Growth Factors

Keywords

  • Calcium
  • Free radicals
  • Ischemia
  • Neurotrophic factor
  • NF-κB
  • Par-4

ASJC Scopus subject areas

  • Anatomy
  • Clinical Biochemistry
  • Cell Biology

Cite this

Mattson, M. P., Culmsee, C., & Zai, F. Y. (2000). Apoptotic and antiapoptotic mechanisms in stroke. Cell and Tissue Research, 301(1), 173-187.

Apoptotic and antiapoptotic mechanisms in stroke. / Mattson, Mark P.; Culmsee, Carsten; Zai, Fang Yu.

In: Cell and Tissue Research, Vol. 301, No. 1, 2000, p. 173-187.

Research output: Contribution to journalArticle

Mattson, MP, Culmsee, C & Zai, FY 2000, 'Apoptotic and antiapoptotic mechanisms in stroke', Cell and Tissue Research, vol. 301, no. 1, pp. 173-187.
Mattson MP, Culmsee C, Zai FY. Apoptotic and antiapoptotic mechanisms in stroke. Cell and Tissue Research. 2000;301(1):173-187.
Mattson, Mark P. ; Culmsee, Carsten ; Zai, Fang Yu. / Apoptotic and antiapoptotic mechanisms in stroke. In: Cell and Tissue Research. 2000 ; Vol. 301, No. 1. pp. 173-187.
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