Growth and Neurotrophic Factors

Nerve growth factor (NGF) is reqnired for snrvival and nenrite ontgrowth of cholinergic nenrons of the basal forebrain. 

The increased number of newly generated cells in the SGZ following Ufe-style modulators, is thought to be due to the increase in cell survival and has been linked to increased protein levels for both BDNF and neurotrophin 3 (NT-3) (Lee et al., 2000, 2002 Duan et al., 2001). Ciliary neurotrophic factor (CNTF) is an acidic protein involved in type-2 astrocyte differentiation. Injection of CNTF into the mouse brain stimulates precursor cell proliferatiou with the CNTF receptor alpha expressed ou GFAP-positive cells of the SVZ (Emsley audHagg,2003). 

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Cytokines and Immunophilins. A large number of inflammatory mediators and related proteins including the cytokines, colony stimulating factors (CSFs), interferons (IFNs), tumor necrosis factors (TNFs), growth factors (see Growth regulators), neurotrophic factors, and immunophilins are found in the mammalian CNS and appear to play a significant role in CNS function both in development and in aspects of brain homeostasis (40—43). 

Biomedical research continues to broaden our understanding of the molecular mechanisms underlining both health and disease. Research undertaken since the 1950s has pinpointed a host of proteins produced naturally in the body that have obvious therapeutic applications. Examples include the interferons and interleukins (which regulate the immune response), growth factors, such as erythropoietin (EPO which stimulates red blood cell production), and neurotrophic factors (which regulate the development and maintenance of neural tissue). 

Table 7.11. Some neurodegenerative diseases for which no current effective therapy exists, and neurotrophic factors known to stimulate growth of neuronal populations affected by these conditions...

C.D. Nandini, N. Itoh, K. Sugahara, Novel 70-kDa chondroitin sul-fate/dermatan sulfate hybrid chains with a unique heterogeneous sulfation pattern from shark skin, which exhibit neuritogenic activity and binding activities for growth factors and neurotrophic factors, J. Biol. Chem. 280 (6) (2005) 4058-4069. 

Conserved dopamine neurotrophic factor (CDNF) is a newly discovered growth factor with a high specificity and activity to promote survival of dopaminergic neurons in vitro and in vivo. CDNF is homologous to an astrocyte-derived growth factor, MANF-1. 

Nerve Growth Factor Neurotrophic Factors Pain and Nociception... 

Many cytokines play a regulatory role in processes other that immunity and inflammation. Neurotrophic factors, such as NGF and BDNF, regulate growth, development and maintenance of various neural populations in the central and peripheral nervous system. EPO stimulates the production of red blood cells from erythroid precursors in the bone marrow. 

IGF-I is widely expressed in the central nervous system. IGF-II is also present, being produced mainly by tissues at vascular interfaces with the brain. Both growth factors, along with insulin, play a number of important roles in the nervous system. They stimulate the growth and development of various neuronal populations and promote neurotrophic effects (discussed later) and may, therefore, be of potential use in the treatment of various neurodegenerative diseases. 

Each neurotrophic factor influences the growth and development of a specific group of neuronal types, with some cells being sensitive to several such factors. Many sustain specific neuronal populations whose death underlines various neurodegenerative diseases. This raises the possibility that these regulatory molecules may be of benefit in treating such diseases. Results from early clinical trials have been at best mixed, but many remain optimistic that neurotrophic factors may provide future effective treatments for some currently incurable neurodegenerative conditions. 

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