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Official Full Name
galanin/GMAP prepropeptide
Background
Galanin is small neuropeptide that functions as a cellular messenger within the central and peripheral nervous systems,;modulating diverse physiologic functions (Mechenthaler, 2008 (PubMed 18500643)).
Synonyms
GAL; galanin prepropeptide; galanin peptides; Galn; galanin , GALN; galanin message associated peptide; GLNN; GMAP; galanin-related peptide; galanin-message-associated peptide; MGC40167; galanin/GMAP prepropeptide; galanin

Galanin, a 29 amino-acid neuropeptide, was isolated in 1983 from porcine intestine by Tatemoto et al. This bioactive peptide distributed widely throughout the central and peripheral nervous system and other tissues. In brain, galanin is synthesized in the dorsal raphe nucleus, locus coeruleus (LC), rostral ventrolateral medulla, the paraventricular nucleus (PVN), central nucleus of the amygdala and the supraoptic nucleus. Besides brain, galanin is also located in the gut and spinal cord. It is involved in a wide range of physiological functions, such as modulating pituitary hormone and insulin release, energy homeostasis, alcohol dependence, neuropathic pain and insulin sensitivity.

As yet, three types of galanin receptors (GalR1, GalR2, and GalR3) have been identified by molecular cloning and characterized pharmacologically in multiple species. Both GalR1 and GalR3 act through Gi/o receptors, inhibiting adenyl cyclase, causing an inhibition of the cAMP response element binding protein (CREB). Distinguished from GalR1 and GalR3, GalR2 activates the pathway of Gq/11, leading to the hydrolysis of inositol phosphate and activation of protein kinase C (PKC) to increase intracellular Ca2+. These different signaling ways suggest that there may be different functions involved (Figure 1).

GalaninFigure 1. Signaling pathways of galanin receptor subtypes.

Galanin has been shown to regulate numerous physiological and pathological processes through interactions with three G-protein coupled receptors, GalR1 through GalR3. The current data has constituted the basis of targeting GalR1, GalR2, and GalR3 for the treatment of various human diseases and pathological conditions, including seizure, Alzheimer’s disease, anxiety, mood disorders, alcohol intake in addiction, pain, metabolic diseases and solid tumors.

Galanin is one of the most inducible neuropeptides. Its biosynthesis is increased 2–10-fold upon axotomy in the periphery and upon seizure activity in the brain. Increased galanin concentrations appear to be neuroprotective and to promote neurogenesis. These observations suggest that agonists of galanin receptors (GalR1–3) may be useful therapeutic agents in neuroprotection. Expression of galanin peptide has been detected in pheochromocytoma, neuroblastic tumors, pituitary adenoma, gastrointestinal cancer, brain tumors, squamous cell carcinoma, melanoma, breast cancer and embryonal carcinoma. In several cancers and tumor cell lines expression of galanin receptors has been also shown. Expression of peptide or receptors has been correlated with tumor stage or subtypes of pituitary adenoma, colon carcinoma, neuroblastic tumors, and squamous cell carcinoma. Galanin treatment has tumor-reducing effects in murine models of gastrointestinal cancer, whereas in animal experiments on adenoma formation, galanin seems to act as a growth factor, promoting both proliferation and tumor formation. In cell culture experiments on tumor cell lines, galanin has shown growth promoting or inhibiting effects. Activation of GalR1 is generally anti-proliferative, whereas activation of GalR2 can have pro- or anti-proliferative effects. Consequently, galanin and its receptors are promising targets for diagnosis and treatment of several types of tumors.

References:

  1. Fang P, et al. Galanin and its receptors: a novel strategy for appetite control and obesity therapy. Peptides, 2012, 36(2):331-339.
  2. Mitsukawa K, et al. Galanin, Galanin Receptors, and Drug Targets// Galanin. Springer Basel, 2010:7-23.
  3. I. Rauch, Barbara Kofler. The Galanin System in Cancer. EXS, 2010, 102:223-241.
  4. T. Hökfelt, K. Tatemoto. Galanin: A Multitalented Neuropeptide. EXS, 2010, 102(102):1.