4.7 Review

CRABP1 in Non-Canonical Activities of Retinoic Acid in Health and Diseases

Journal

NUTRIENTS
Volume 14, Issue 7, Pages -

Publisher

MDPI
DOI: 10.3390/nu14071528

Keywords

CRABP1; retinoic acid; neurodegeneration; inflammation; metabolism; cancer; human disease; non-canonical; MAPK; CAMKII

Funding

  1. NIH [DK54733, DK60521, F31DK123999]
  2. Dean's Commitment and the Distinguished McKnight Professorship of the University of Minnesota

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Cellular Retinoic Acid Binding Protein 1 (CRABP1) plays an important role as a mediator of non-canonical activities of retinoic acid and is associated with stem cell proliferation, cancers, adipocyte health, neuro-immune regulation, heart, and motor neuron diseases. Abnormal CRABP1 is potentially associated with human diseases such as cancer, neurodegenerative diseases, and immune diseases.
In this review, we discuss the emerging role of Cellular Retinoic Acid Binding Protein 1 (CRABP1) as a mediator of non-canonical activities of retinoic acid (RA) and relevance to human diseases. We first discuss the role of CRABP1 in regulating MAPK activities and its implication in stem cell proliferation, cancers, adipocyte health, and neuro-immune regulation. We then discuss an additional role of CRABP1 in regulating CaMKII activities, and its implication in heart and motor neuron diseases. Through molecular and genetic studies of Crabp1 knockout (CKO) mouse and culture models, it is established that CRABP1 forms complexes with specific signaling molecules to function as RA-regulated signalsomes in a cell context-dependent manner. Gene expression data and CRABP1 gene single nucleotide polymorphisms (SNPs) of human cancer, neurodegeneration, and immune disease patients implicate the potential association of abnormality in CRABP1 with human diseases. Finally, therapeutic strategies for managing certain human diseases by targeting CRABP1 are discussed.

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