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p62/SQSTM1, a Central but Unexploited Target: Advances in Its Physiological/Pathogenic Functions and Small Molecular

Ying Chen1, Qi Li2, Qihang Li2

  • 1Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, People's Republic of China.

Journal of Medicinal Chemistry
|April 24, 2020
PubMed

Insights

The p62/SQSTM1 protein regulates autophagy and stress responses. Its abnormal expression links to diseases like cancer and neurodegeneration, suggesting it as a therapeutic target.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • p62/SQSTM1 is an adaptor protein crucial for selective autophagy, targeting aggregate-prone proteins for degradation.
  • It acts as a stress-induced scaffold protein, activating Nrf2 to combat oxidative stress.
  • p62's interactions with cell differentiation and proliferation pathways highlight its role in cell survival and apoptosis.

Purpose of the Study:

  • To review the multifaceted roles of p62/SQSTM1 in cellular processes.
  • To elucidate the association between p62/SQSTM1 and various human diseases.
  • To explore novel diagnostic and therapeutic strategies targeting p62/SQSTM1.

Main Methods:

  • Literature review of studies on p62/SQSTM1 function and disease association.
  • Analysis of the molecular mechanisms linking p62/SQSTM1 to autophagy, oxidative stress, and disease pathogenesis.
  • Synthesis of current research on p62/SQSTM1 as a potential therapeutic target.

Main Results:

  • p62/SQSTM1 is implicated in the degradation of toxic protein aggregates via autophagy.
  • Its role in Nrf2 activation is critical for cellular defense against oxidative stress.
  • Aberrant p62/SQSTM1 expression or SQSTM1 gene mutations are linked to cancer, neurodegenerative diseases, and other pathologies.

Conclusions:

  • p62/SQSTM1 is a key mediator in cellular homeostasis, with significant implications in disease development.
  • Understanding p62/SQSTM1's functions offers potential for developing targeted therapies for diseases like cancer and Alzheimer's.
  • Regulating p62/SQSTM1 expression presents a promising avenue for future diagnostic and therapeutic interventions.

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