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Activation of the mTOR pathway promotes neurite growth through upregulation of CD44 expression

Jiwei Zhang1, Wenjuan Gan1, Ru Peng2

  • 1Department of Pathology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, 215123, China.

The Journal of International Medical Research
|June 21, 2023
PubMed
Abstract

Insights

Activating the mammalian target of rapamycin (mTOR) pathway promotes neuronal regeneration by upregulating cluster of differentiation 44 (CD44) expression, enhancing neurite growth.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Neuronal regeneration is crucial for recovery from neurological damage.
  • The mammalian target of rapamycin (mTOR) pathway plays a role in cell growth and survival.
  • Understanding the mechanisms of neuronal axon growth is essential for developing therapeutic strategies.

Purpose of the Study:

  • To elucidate the intrinsic mechanism by which the mammalian target of rapamycin (mTOR) pathway is activated.
  • To investigate the role of mTOR pathway activation in promoting neuronal axon growth.
  • To explore the relationship between phosphatase and tensin homolog (PTEN), cluster of differentiation 44 (CD44), and neuronal regeneration.

Main Methods:

  • Human neuroblastoma SH-SY5Y cells were differentiated into a neuronal-like state using all-trans retinoic acid (ATRA).
  • Phosphatase and tensin homolog (PTEN) and cluster of differentiation 44 (CD44) were downregulated using RNA interference (RNAi).
  • Gene and protein expression levels of PTEN, mTOR, pS6k, and CD44 were analyzed using RT-PCR and western blot assays. Neurite length was measured to assess axonal growth.

Main Results:

  • Downregulation of PTEN led to significant upregulation of mTOR and pS6k protein expression.
  • PTEN interference also resulted in increased CD44 transcription levels.
  • Cells with downregulated PTEN exhibited significantly longer neurites, and CD44 expression positively correlated with neurite growth.

Conclusions:

  • Activation of the mTOR pathway promotes neurite outgrowth and neuronal regeneration.
  • Upregulation of CD44 expression is a key mechanism through which the mTOR pathway enhances axonal growth.
  • Targeting the mTOR-CD44 axis presents a potential therapeutic strategy for promoting neuronal repair.
Keywords:
Axonal growthCD44Nerve regenerationmTOR pathway

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