Fig. 1

Linear structure, functional domains and key modifications of GFAP-α. GFAP-α is the most abundant subtype, which contains the head, core domain, and tail. The core domain is composed of the coil domain (1A, 1B, 2A, 2B) and linker regions (L1, L1,2 and L2). The expression of GFAP protein is inhibited by a number of agents. Prosaptide, a peptide derived from a 14-amino-acid (Thr-D–Ala–Leu–Ile–Asp–Asn–Asn–Ala–Thr–Glu–Glu–Ile–Leu–Tyr) neurotrophic sequence of human glycoprotein prosaposin, which can cross BBB or BCB to exert its GFAP-suppression effects and thereby exert its therapeutic effects. In addition, WF-A, a steroidal lactone isolated from Ayurvedic medicine Winter cherry, also have been studied that it can inhibit GFAP and the related IF protein vimentin via the covalent modification of the single Cys-294 of GFAP. And then, Ibudilast, a board-spectrum PDE inhibitor, was unexpectedly found to also inhibit methamphetamine-induced GFAP upregulation and gliosis. Furthermore, a number of drug-like agents have reported to have suppressed effects either in GFAP protein expression or gliosis induction, varying from aspirin/acetylsalicylic acid, clomipramine to curcumin (unknown exact mechanism). L1 Linker 1; BBB blood brain barrier, BCB blood cerebrospinal fluid barrier, WF-A Withaferin A, IF intrinsic factor, PDE Phosphodiesterase