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Druggability of mortalin for cancer and neuro-degenerative disorders

Custer C Deocaris1, Wen-Jing Lu, Sunil C Kaul

  • 1National Institute of Advanced Industrial Science & Technology, Central 4, 1-1-1 Higashi, Tsukuba, Ibaraki 305 8562, Japan.

Current Pharmaceutical Design
|August 28, 2012
PubMed

Insights

Mortalin, a stress chaperone protein, has dual roles in cell aging and lifespan. Its levels are linked to cancer and neurodegenerative diseases, suggesting it could be a therapeutic target.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Gerontology

Background:

  • Mortalin is a stress chaperone belonging to the Hsp70 family.
  • It plays a role in cellular senescence and lifespan.
  • Two mouse mortalin alleles (mot-1 and mot-2) exhibit contrasting effects on cell aging.

Purpose of the Study:

  • To investigate the contrasting roles of mortalin alleles in cellular processes.
  • To explore the involvement of mortalin in human diseases like cancer and neurodegeneration.
  • To assess the therapeutic potential of targeting mortalin.

Main Methods:

  • Genetic studies in mouse models.
  • Analysis of mortalin expression in human cells.
  • Correlation of mortalin levels with disease states.

Main Results:

  • Mouse mortalin alleles mot-1 and mot-2 show differing impacts on cell senescence and lifespan.
  • Human mortalin functions similarly to the lifespan-extending mouse mot-2.
  • Mortalin is upregulated in cancer cells, promoting carcinogenesis.
  • Mortalin deficiency is observed in age-related brain disorders.

Conclusions:

  • Mortalin exhibits context-dependent functions in cellular aging.
  • Its dysregulation is implicated in both cancer and neurodegenerative diseases.
  • Mortalin represents a potential bidirectional therapeutic target for these conditions.

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