Cerebellin and Analogs

Definition
Cerebellin (CER) is a neuromodulatory hexadecapeptide that originates from the precursor protein precerebellin (Cbln1) and modulates synaptic structure formation in the central nervous system1.

Discovery
Cerebellin was first identified and purified from rat cerebellum in 1984 by HPLC techniques2.

Classification
Cerebellin is a neuropeptide generated from the precursor, precerebellin which has four isoforms, Cbln1-41.

Structural Characteristics
Cerebellin is a hexadecamer of primary amino acid sequence NH(2)-Ser-Gly-Ser-Ala-Lys-Val-Ala-Phe-Ser-Ala-Ile-Arg-Ser-Thr-Asn-His- OH3.

Mode of action
One of the functions of cerebellin is to enhance secretory activity of human adrenal gland. It does this by exerting a sizable secretagogue action on both cortex and medulla of human adrenals4. The peptide directly stimulates catecholamine release via the adenylate cyclase/protein kinase A-dependent signaling pathway and the mechanism underlying the adrenocortical stimulatory effect of cerebellin is indirect and probably involves the release of catecholamines, which in turn enhances steroid-hormone secretion4.

Functions
Cerebellin is widely distributed in the central nervous system where it exerts neuromodulatory functions such as synaptic structure formation4. It is also expressed in the peripheral tissues such as pancreas and adrenal glands where it regulates catecholamine secretion4.

References
1.Strowski MZ, Kaczmarek P, Mergler S, Wiedenmann B, Domin D, Szwajkowski P, Wojciechowicz T, Skrzypski M, Szczepankiewicz D, Szkudelski T, Rucinski M, Malendowicz LK, Nowak KW (2009). Insulinostatic activity of cerebellin - Evidence from in vivo and in vitro studies in rats. Regul Pept, EPub ahead of print.
2.Slemmon JR, Blacher R, Danho W, Hemstead JL, Morgan JI (1984). Isolation and sequencing of two cerebellum-specific peptides. Proc Natl Acad Sci USA, 81:6866-6870.
3.Urade Y, Oberdick J, Molinar-Rode R, Morgan JI (1991). Precerebellin is a cerebellum-specific protein with similarity to the globular domain of complement C1q B chain. Proc Natl Acad Sci U S A, 88(3), 1069-73.
4.Mazzocchi G, Andreis PG, De Caro R, Aragona F, Gottardo L, Nussdorfer GG (1999). Cerebellin enhances in vitro secretory activity of human adrenal gland. J Clin Endocrinol Metab, 84(2), 632-5.