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Sortilins in neurotrophic factor signaling.

S Glerup1, A Nykjaer, C B Vaegter

  • 1Danish Research Institute of Translational Neuroscience DANDRITE, Nordic EMBL Partnership, and The Lundbeck Foundation Research Center MIND, Department of Biomedicine, University of Aarhus, Ole Worms Allé 3, 8000, Aarhus C, Denmark.

Handbook of Experimental Pharmacology
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Summary
This summary is machine-generated.

The sortilin receptor family plays roles in cell signaling and protein sorting, impacting neuronal health and diseases like Alzheimer's. These receptors are also implicated in coronary artery disease and type-2 diabetes.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Sortilin receptors (including sortilin, SorLA, SorCS1-3) are type-I transmembrane proteins.
  • Predominantly expressed in neuronal tissues, they also appear in hepatocytes and immune cells.
  • Their functions involve both cell signaling and intracellular protein sorting.

Purpose of the Study:

  • To explore the complex roles of sortilin receptors.
  • To understand their involvement in neuronal signaling and protein metabolism.
  • To highlight their association with neurological and systemic diseases.

Main Methods:

  • Review of existing literature on sortilin family receptors.
  • Analysis of genome-wide association studies (GWAS).
  • Examination of sortilin involvement in neurotrophin signaling and amyloid precursor protein (APP) processing.

Main Results:

  • Sortilins are crucial for signaling by pro- and mature neurotrophins, affecting neuronal viability.
  • They play a role in the processing and metabolism of amyloid precursor protein (APP).
  • GWAS link sortilin family members to Alzheimer's disease, bipolar disorder, coronary artery disease, and type-2 diabetes.

Conclusions:

  • Sortilin receptors are multifunctional proteins with significant roles in neuronal and non-neuronal systems.
  • Dysregulation of sortilins is associated with major human diseases, indicating therapeutic potential.
  • Further research into sortilin biology is warranted given their complex functions and disease links.