Adventures with neurosecretory cytokines

Armen Galoyan has authored a remarkable sequel to his earlier book Biochemistry of Novel Cardioactive Hormones and Immunomodulators of the Functional System Neurosecretory Hypothalamus–Endocrine Heart. His new book, Brain Neurosecretory Cytokines: Immune Response and Neuronal Survival, offers a continuation of his profound observations of this burgeoning field.Galoyan begins by describing the phenomenon of interleukin (IL) biosynthesis and secretion by the hypothalamic supraoptic (NSO) and paraventricular (NPV) neurons. This discovery was the first suggestion that interleukins are a neurosecretion of hypothalamic nuclei and was later supported by experimental results. The presence of IL-1α, IL-β, IL-2, IL-6 and tumor necrosis factor-α has been demonstrated in neurosecretory granules of the hypothalamo–neurohypophyseal system.Next, the reader is introduced to the discovery of novel cytokines and hormonal systems of the neurosecretory hypothalamus. The NPV and NSO produce proline-rich peptides (PRPs). Four PRPs were isolated and their primary structures deciphered. Galoyan and his colleagues discovered and demonstrated the primary structure of immunophilins (containing 107 amino acid residues) that act as receptors in the hypothalamus for the immunosuppressor FK506. The discovery of the existence of these proteins that possess peptidyl-prolyl-cis-transisomerase activity has set new challenges for understanding the role of IL in the NSO and NPV neurons of the hypothalamus. The concept of the formation of immunophilin–ligand complexes between immunophilin and the coronary-active neurohormone ‘C’ and thymosin β4 (residues 1–39), which participate in the biosynthesis of IL-2 in the neurosecretory cells, is also developed. These data add significantly to knowledge of the biochemical mechanisms of immune system regulation in general, and hypothalamo–hypophyseal–adrenal axis regulation in particular, thus enriching our understanding of the relationship between the systemic immune system, the brain immune system, and the hypothalamo–hypophyseal–adrenal axis.The powerful antibacterial, antiviral and immunological properties of PRP-1 are covered in the book. Investigations of PRP-1 regulatory influence on thymocyte differentiation in philo-ontogenesis and myelopoiesis (under normal conditions and during cyclophosphamide-induced lymphocytopenia with Pseudomonas aeruginosa) are of great theoretical and practical importance. Galoyan's group has also studied the effect of PRP on thymocyte differentiation in vivo and in vitro using mouse fetal and neonatal thymus gland. PRP-1 increases generation of CD4+ and CD8+ thymocytes (purified with anti-CD8 antibody) both in vivo and in vitro, showing that PRP-1 modulates thymocytic development (proliferation, maturation and generation of surface major histocompatibility complex gene products) during fetal life.Galoyan describes the potent antineurodegenarative properties of PRP-1 that are shown after neurological damage caused by, for example, intoxication with snake venom, crush syndrome, spinal cord hemisection and aluminum neurotoxicity. PRPs restore neuronal function and morphology and prevent scar formation after spinal cord hemisection, indicating possibilities for healing traumatic injuries and other neurological insults in the spinal cord and other sections of the nervous system.As well as its role in neurodegeneration, PRP-1 also appears to have an impact on tumor cells. Electron-microscopy has been used to observe tissues from animals exposed to ionizing radiation; these results are presented in the book.Galoyan ends the book by describing the biochemical mechanism of PRP action. PRP-1 in the nanomolar–picomolar range stimulates biosynthesis of glial fibrillary acidic protein in astrocyte culture through the trkB receptor, similar to the effect of neural growth factor. Glial fibrillary acidic protein inhibits activity of effectors caspase-6 and caspase-9, while activating caspase-2 and caspase-6. Considerable additional work has been carried out with membrane phospholipids to demonstrate the antioxidative, antiradical properties of PRP-1, which have an important role in immune response and neuronal survival.In summary, Brain Neurosecretory Cytokines is an excellent book, a veritable goldmine of information, at the cutting edge of neuroscience. It should stimulate ideas for future directions in neuroscience for years to come. This volume should be highly useful for medical libraries, neuroscientists, endocrinologists and graduate students in these fields.