adventures with neurosecretory cytokines

Update TRENDS in Endocrinology and Metabolism Vol.16 No.6 August 2005 251

Book Reviews

Adventures with neurosecretory cytokinesBrain Neurosecretory Cytokines: Immune Response and Neuronal Survival by Armen A. Galoyan. Kluwer Academic/Plenum

Publishers, 2004. US$115.00 (viiiC188 pages) ISBN 0 306 48337 8

Arthur S. Brecher

Department of Chemistry, Bowling Green State University, Bowling Green, OH 43403, USA

Armen Galoyan has authored aremarkable sequel to his earlier bookBiochemistry of Novel CardioactiveHormones and Immunomodulators ofthe Functional System NeurosecretoryHypothalamus–Endocrine Heart. Hisnew book, Brain Neurosecretory Cyto-kines: Immune Response and Neu-ronal Survival, offers a continuation

burgeoning field.Galoyan begins by describing the phenomenon of

interleukin (IL) biosynthesis and secretion by the hypo-thalamic supraoptic (NSO) and paraventricular (NPV)neurons. This discovery was the first suggestion thatinterleukins are a neurosecretion of hypothalamic nucleiand was later supported by experimental results. Thepresence of IL-1a, IL-b, IL-2, IL-6 and tumor necrosisfactor-a has been demonstrated in neurosecretory gran-ules of the hypothalamo–neurohypophyseal system.

Next, the reader is introduced to the discovery of novelcytokines and hormonal systems of the neurosecretoryhypothalamus. The NPV and NSO produce proline-richpeptides (PRPs). Four PRPs were isolated and their prim-ary structures deciphered. Galoyan and his colleaguesdiscovered and demonstrated the primary structure ofimmunophilins (containing 107 amino acid residues) thatact as receptors in the hypothalamus for the immunosup-pressor FK506. The discovery of the existence of theseproteins that possess peptidyl-prolyl-cis-transisomeraseactivity has set new challenges for understanding the roleof IL in the NSO and NPV neurons of the hypothalamus.The concept of the formation of immunophilin–ligandcomplexes between immunophilin and the coronary-activeneurohormone ‘C’ and thymosin b4 (residues 1–39), whichparticipate in the biosynthesis of IL-2 in the neuro-secretory cells, is also developed. These data addsignificantly to knowledge of the biochemical mechanismsof immune system regulation in general, and hypotha-lamo–hypophyseal–adrenal axis regulation in particular,thus enriching our understanding of the relationshipbetween the systemic immune system, the brain immunesystem, and the hypothalamo–hypophyseal–adrenal axis.

The powerful antibacterial, antiviral and immuno-logical properties of PRP-1 are covered in the book.Investigations of PRP-1 regulatory influence on thymocytedifferentiation in philo-ontogenesis and myelopoiesis

Corresponding author: Brecher, A.S. (artbrec@bgsu.edu).Available online 5 July 2005

www.sciencedirect.com

(under normal conditions and during cyclophosphamide-induced lymphocytopenia with Pseudomonas aeruginosa)are of great theoretical and practical importance. Galoyan’sgroup has also studied the effect of PRP on thymocytedifferentiation in vivo and in vitro using mouse fetal andneonatal thymus gland. PRP-1 increases generation ofCD4C and CD8C thymocytes (purified with anti-CD8antibody) both in vivo and in vitro, showing that PRP-1modulates thymocytic development (proliferation, matu-ration and generation of surface major histocompatibilitycomplex gene products) during fetal life.

Galoyan describes the potent antineurodegenarativeproperties of PRP-1 that are shown after neurologicaldamage caused by, for example, intoxication with snakevenom, crush syndrome, spinal cord hemisection andaluminum neurotoxicity. PRPs restore neuronal functionand morphology and prevent scar formation after spinalcord hemisection, indicating possibilities for healingtraumatic injuries and other neurological insults in thespinal cord and other sections of the nervous system.

As well as its role in neurodegeneration, PRP-1 alsoappears to have an impact on tumor cells. Electron-microscopy has been used to observe tissues from animalsexposed to ionizing radiation; these results are presentedin the book.

Galoyan ends the book by describing the biochemicalmechanism of PRP action. PRP-1 in the nanomolar–picomolar range stimulates biosynthesis of glial fibrillaryacidic protein in astrocyte culture through the trkBreceptor, similar to the effect of neural growth factor.Glial fibrillary acidic protein inhibits activity of effectorscaspase-6 and caspase-9, while activating caspase-2 andcaspase-6. Considerable additional work has been carriedout with membrane phospholipids to demonstrate theantioxidative, antiradical properties of PRP-1, whichhave an important role in immune response andneuronal survival.

In summary, Brain Neurosecretory Cytokines is anexcellent book, a veritable goldmine of information, at thecutting edge of neuroscience. It should stimulate ideas forfuture directions in neuroscience for years to come. Thisvolume should be highly useful for medical libraries,neuroscientists, endocrinologists and graduate studentsin these fields.

1043-2760/$ - see front matter Q 2005 Elsevier Ltd. All rights reserved.

doi:10.1016/j.tem.2005.06.008