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[Apoptosis or programmed cell death: regulatory and pathophysiological mechanisms]

F Silvestris, D Ribatti, B Nico

    Annali Italiani Di Medicina Interna : Organo Ufficiale Della Societa Italiana Di Medicina Interna
    |January 1, 1995
    PubMed
    Summary

    Apoptosis, programmed cell death, is crucial for eliminating abnormal cells. Its deregulation is implicated in diseases like cancer, HIV, and neurodegenerative conditions, but therapeutic applications remain unexplored.

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    Area of Science:

    • Cell Biology
    • Molecular Biology
    • Genetics

    Background:

    • Apoptosis is a genetically encoded, active cell death process essential for removing abnormal or unwanted cells.
    • It involves molecular cascades, nucleolysis by endonucleases, and interactions between membrane receptors and cytoplasmic proteins.
    • Key regulators include Fas, p53, c-myc, and bcl-2, which modulate apoptosis based on stimuli and cell state.

    Purpose of the Study:

    • To explore the role of apoptosis deregulation in various diseases.
    • To highlight the implications of apoptosis in cancer, HIV infection, autoimmune disorders, and neurodegenerative diseases.
    • To review the current understanding of apoptosis-related gene deregulation in disease pathogenesis.

    Main Methods:

    • Review of existing literature on apoptosis molecular mechanisms.

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  • Analysis of genetic regulation of apoptosis-related proteins.
  • Examination of the role of apoptosis in specific disease contexts.

    • Main Results:

    • Deregulation of apoptosis-related genes is linked to tumor growth, such as bcl-2 overexpression in lymphomas inhibiting apoptosis.
    • Fas gene activation in HIV-infected T cells exacerbates lymphopenia by increasing normal apoptosis.
    • Altered apoptosis mechanisms are postulated in autoimmune diseases (e.g., lupus) and neurodegenerative conditions (e.g., Alzheimer's disease).

    Conclusions:

    • Genetic deregulation of apoptosis is implicated in the pathogenesis of diverse diseases.
    • While apoptosis plays a role in conditions like cancer and neurodegeneration, its therapeutic exploitation is not yet established.
    • Further research is needed to understand and potentially target apoptosis for therapeutic benefit.