Cellular RA Binding Proteins (CRABPs) Signalosomes: Targeting Dynamic Signal Regulation in Managing Neurodegeneration
Year: 2026
Type: article
Abstract: Vitamin A (retinol) and its derivatives, collectively referred to as retinoids, are gaining increasing appreciation in managing neurodegenerative diseases such as Alzheimer’s Disease (AD), Amyotrophic Lateral Sclerosis (ALS), Huntington Disease (HD) and Parkinson’s Disease (PD) [1-12]. Retinoic Acid (RA) is the principal active metabolite of vitamin A and has profound roles in numerous biological processes and organ systems, including differentiation, proliferation, cell death programs, development, immunity, the Central Nervous System (CNS) and the visual system, etc [13]. RA exerts its effects by two major mechanisms, binding nuclear RA Receptors (RARs) to regulate gene expression in the nucleus (canonical mechanism) and binding its cytosolic receptors, Cellular RA Binding Proteins (CRABPs) for metabolism or cytosolic signaling [14]. In addition, RA has also been reported to directly modulate kinases such as PKC or certain activity of extranuclear RARs (reviewed in-depth elsewhere) [15]. In the cytoplasm, CRABP2 binds RA to facilitate its metabolism, whereas CRABP1 binds RA to elicit its regulatory activities in multiple cytosolic signaling pathways [16-18]. The CRABP1-targeted cytosolic signaling complexes are named CRABP1-signalosomes and are referred to as the main non-canonical mediators of RA. This commentary focuses on the CRABP1-mediated non-canonical activities of RA, which are characterized by three features – independence from RARs, cytosolic localization and rapid (minutes) actions
Authors: Jennifer Nhieu, Li-Na Wei
Institution: University of Minnesota
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W7125653253