Novel functions of folate receptor alpha in CNS development and diseases

Abstract

Abstract(Folate receptor alpha), a GPI-anchored protein is critical for embryonic development. Disruption of both FRα alleles in mice results in pups with a range of malformations and is lethal to the embryos at the time of neural tube closure. Recent body of evidences emphasizes its role in neural tube defects, cerebral folate deficiency, autism and autism spectrum disorders. Circulating autoantibodies against FRα and cerebral folate deficiency appear to play a crucial role in the cause and pathogenesis of a particular subgroup of autism spectrum disorders with co-existing neurological deficits. Since FRα is known to be over-expressed in cancer cells, it has found a novel theranostic role in cancer diagnosis and treatment by using FA-conjugated imaging agents as diagnostic tools and FA-conjugated nanotherapeutics and immunotherapy for cancer. This review highlights some recent advances and novel roles of FRα other than it being just a folate transporter.

Folate Receptor Alpha Autoantibodies in Autism Spectrum Disorders: Diagnosis, Treatment and Prevention

“…The most characterized of these receptors is folate receptor alpha (FRα). As extracellular receptors, FRα, FRβ, FRγ and FRδ function as transporters of folate across different target tissues [ 33 , 34 ]. FRα can also act as a transcription factor [ 33 ].…”

“…As extracellular receptors, FRα, FRβ, FRγ and FRδ function as transporters of folate across different target tissues [ 33 , 34 ]. FRα can also act as a transcription factor [ 33 ]. Other transporters of folate include the reduced folate carrier (RFC), which requires high local concentrations (micromolar) of biologically active reduced forms of folates, and the proton-coupled folate transporter (PCFT), which can only transport folates and folic acid under acidic conditions and is the primary transporter involved in folate absorption in the gut [ 35 ].…”

Activated Microglia in the Brain: Mitochondrial and Cell Membrane-Associated Targets for Positron Emission Tomography

“…Homologies between the receptor isoforms are high with only small differences in the pharmacodynamically relevant structures. However, FR3 is a soluble receptor and, recently, a role of FR1 was described as a transcriptionally relevant protein, which may interact with nuclear structures following internalization [121] [122].…”

Multifunctional Hybrid Silica Nanoparticles with a Fluorescent Core and Active Targeting Shell for Fluorescence Imaging Biodiagnostic Applications

“…Folic acid (FA) is a targeting group of particular interest because it is readily available and stable over a broad range of temperatures and pH values, does not trigger an immunologic response, and retains its ability to specifically bind to folate receptors, even when linked to other molecules 15. Folic acid conjugated nanoparticles bind to cell membrane folate receptors by an active targeting mechanism 36,37. As folate receptors are overexpressed in the membranes of many cancer cell types and tissues, including ovarian, endometrial, and kidney cancer,36–39 folic acid conjugated nanoparticles carrying therapeutic agents are expected to increase their delivery efficiency and avoid side effects, as the exposure of healthy cells to the anticancer agent can be minimized.…”

“…Folic acid conjugated nanoparticles bind to cell membrane folate receptors by an active targeting mechanism 36,37. As folate receptors are overexpressed in the membranes of many cancer cell types and tissues, including ovarian, endometrial, and kidney cancer,36–39 folic acid conjugated nanoparticles carrying therapeutic agents are expected to increase their delivery efficiency and avoid side effects, as the exposure of healthy cells to the anticancer agent can be minimized.…”