Table 1.
Summary of transporters and receptors involved in transport of peptides and proteins at blood–cerebrospinal fluid (CSF) barriers (BCSFB).
| Transporter/Receptors | Expression | Localization | Endogenous Substrate | Direction | Function | |
|---|---|---|---|---|---|---|
| Peptide transporter (PTR) family | PEPT2/SLC15A2 | mRNA (r) [74,75] | A of CPECs (r) [76] | Di-/tripeptide [73] | Efflux, CSF→luminal [76] | Removal of neuropeptides, peptide fragments, and peptide-like drugs from CSF [76,77] |
| P-glycoprotein | Pgp/MDR1 | mRNA and protein (r, m h) [82] | A of CPECs (h) [81] | Aβ [80,83] | Efflux, CSF→luminal [80,83] | - |
| Transferrin (Tf) receptor | TfR | mRNA and protein (r) [90] | CPECs (h) [89], (r) [85], (m) [86], vesicles around nuclei of CPECs (r) [90] | Tf [86,91] | Unidirectional uptake (luminal→CP epithelium) [91] | Uptake of Tf bound iron into CPECs and slow release of iron to CSF [91] |
| Insulin receptor | mRNA (r) [93] | CPECs (r) [94,95] | Insulin [94] | Luminal→CSF [94] | May transport insulin from the blood into the CSF with intermediate compartment and saturable process [94] | |
| Insulin-like growth factor receptors | IGF1R | mRNA (r) [97], (r fetus) [98] | CPECs (r) [95], (h) [101], on surface of CPECs (p) [102] | IGF-I, IGF-II, insulin [96] | Luminal→CSF [104] | Mediates effects of IGF-I and IGF-II [102] |
| IGF2R | mRNA (r) [99,100] | Intracellular of CPECs (p) [102], epithelium and endothelium CP (infant r) [103] | IGF-I, IGF-II [96] | - | - | |
| Low density lipoprotein (LDL) receptor | LDLR | - | A of CPECs (h) [79] | LDL [107] | - | - |
| LDL receptor-related proteins (LRPs) | LRP1 (LRP/α2-macroglobulin receptor) | mRNA and protein (h) [108,112], (r) [109], mRNA (r) [110], protein (r) [111] | Diffuse cellular of CPECs (r) [113], CPECs (h) [79] | α2-macroglobulin [35], Aβ [35,111,112] | Efflux (CSF→luminal) [109] | May involve in the clearance of protease/α2-macroglobulin complexes from the CSF [35] Maintains brain homeostasis of Aβand partly mediates the elimination of Aβ from CSF [111,112] May associate with apolipoprotein E (apoE) to influence the severity of cerebral amyloid angiopathy and Alzheimer’s disease [108] |
| LRP2 (megalin/glycoprotein 330) | mRNA and protein (r) [109,117] | A of CPECs (r) [109,116], CPECs and ventricular ependyma (h) [79] | Leptin [120], IGF-I [104,121], ApoJ [119] | Bidirectional transport [35] | Mediates entry of leptin into CSF across CP [120] Mediates penetration of peripheral IGF-I in the CSF and mediates IGF-I-induced clearance of Aβ [121] Bind with ApoJ and mediates clearance of Aβ1-40-apoJ from CSF [119] |
|
| LRP8 (ApoE receptor 2) | mRNA (r) [122] | CPECs (r) [122], (m) [123] | ApoE [122], selenoprotein P (Sepp1) [123] | - | May involve in the uptake of ApoE phospholipid discoidal particles or ApoE-enriched high-density lipoprotein in brain [122] Facilitates uptake of Sepp1 [123] |
|
| Neonatal Fc receptor | FcRn | mRNA (r) [35] | Diffuse cellular of CPECs (r) [35,126], CPECs (monkey, r, m) [128] | IgG [126] | - | May mediate transcytosis of IgG [126] |
CP: choroid plexus, b: basolateral side, a: abluminal/apical side, h: human, r: rats, m: mice, p: porcine, –: not reported.