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Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection

Mikhail V Voronin1, Elena V Abramova1, Ekaterina R Verbovaya1

  • 1Department of Pharmacogenetics, FSBI "Zakusov Institute of Pharmacology", Baltiyskaya Street 8, 125315 Moscow, Russia.

International Journal of Molecular Sciences
|January 8, 2023
PubMed

Insights

This review explores how targeting chaperone proteins, like Sigma1R, can break disease cycles in neurodegenerative conditions. Activating Sigma1R offers a promising neuroprotective strategy for diseases such as Alzheimer's and Parkinson's.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Neurodegenerative diseases share a common pathological pathway: protein misfolding.
  • Current treatments are largely symptomatic, failing to address underlying disease mechanisms.
  • Chaperone proteins, involved in protein folding, offer a potential therapeutic target.

Purpose of the Study:

  • To review endoplasmic reticulum stress (ER stress) and unfolded protein response (UPR) mechanisms in neurodegenerative diseases.
  • To analyze the roles of BiP and Sigma1R chaperones in Alzheimer's, Parkinson's, ALS, and Huntington's diseases.
  • To evaluate the neuroprotective potential of Sigma1R ligand activation.

Main Methods:

  • Literature review of clinical and experimental studies.
  • Analysis of endoplasmic reticulum stress and unfolded protein response pathways.
  • Examination of chaperone interactions, specifically Sigma1R and BiP.

Main Results:

  • Protein misfolding is a key factor in neurodegeneration.
  • Sigma1R chaperone activation demonstrates neuroprotective effects in preclinical models.
  • Interactions between Sigma1R and BiP signaling pathways are crucial for neuroprotection.

Conclusions:

  • Pharmacological regulation of chaperone function is feasible.
  • Ligand activation of Sigma1R presents a viable neuroprotective strategy.
  • Further research is needed on the interplay between Sigma1R and BiP in cellular mechanisms.
Keywords:
BiPER stressIRE1αSigma1Rchaperonesneurodegenerative diseasesneuroprotectionprotein foldingunfolded protein response

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