Brief Insight about Cerebral Cortex and Possible Role of FG Loop Peptide in Neurological Disorders

Abstract

The human nervous system arises from the ectoderm which one of the three distinct embryonic germ layers that arise in the third week after conception. The cerebral cortex is formed from neuroepithelial cells (NECs). In humans, NEC proliferation begins in the 4th week of development in the neural plate. NECs proliferate in a symmetric fashion (one stem cell divides into two stem cells) until neural tube closure is complete. Afterwards, proliferation changes to asymmetric division in which one stem cell produces one stem cell and one neuron. The differentiated neurons are located in the periphery (primordial plexiform layer or preplate PP) and as a consequence, the stem cells are placed in the deep germinative zone called the ventricular zone (VZ).  In early developmental stages when the distance between the VZ and PP is short, the neurons move by somal translocation (nucleokinesis). Nucleokinesis occurs by the neuron extending a process toward the PP meningeal surface, and the nucleus moves toward the surface as the ventricular process shortens and is detached from the ventricle. The FG loop peptide (FGL, EVYVVAENQQGKSKA), is a neural cell adhesion molecule-mimetic peptide (NCAM – mimetic peptide).   Neural cell adhesion molecule NCAM is a cell surface glycoprotein expressed mainly in three isoforms, NCAM120, NCAM140 and NCAM180, named according to their apparent molecular weights. Extracellularly, all three isoforms consist of five Ig-like modules followed by two fibronectins type III (FN3) modules. NCAM signal interacts through its growth factor receptors including fibroblast growth factor receptor (FGFR). The FGFR-1 binding site of NCAM is a 15 amino acid small loop peptide that is is called the FGL peptide. NCAM plays an important role in the nervous system in development, plasticity and learning and memory.    FGL has been shown to rapidly enter the bloodstream, to penetrate the blood–brain barrier, and to circulate within the cerebrospinal fluid upon systemic administration. FGL was reported to be the most promising NCAM mimetic peptide for clinical translation