Pedersen WA, Wan R, Zhang P, Mattson MP. Urocortin, but not urocortin II, protects cultured hippocampal neurons from oxidative and excitotoxic cell death via corticotropin-releasing hormone receptor type I. J Neurosci. 2002 Jan 15;22(2):404-12. PubMed.
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The observation that, in vitro, urocortin provides neuroprotection to vulnerable neurons may have some therapeutic implications in Alzheimer's disease (AD). However, these implications are not clear-cut, since other studies have shown that administering urocortin receptor antagonists can attenuate the neural damage in response to focal cerebral ischemia in vivo. While the authors did quantify the CNS expression of urocortin receptors, it would be of interest to know the tissue concentrations of urocortin relative to specific disease states, other growth factors, and age.
There is evidence that AD is associated with aberrant entry of neurons into the cell cycle. Urocortin receptor expression is higher in the regressing corpus luteum than in the functioning corpus luteum, report Muramatsu et al. 2001. Urocortin has been shown to inhibit melanoma tumor growth (Carlson et al., 2001). In addition, it is not present in the colonic mucosa until after the fetal and neonatal period, the time of most rapid tissue development (Muramatsu et al., 2000). Conversely, urocortin receptor density in the CNS is greatest during early development (De Souza, 1995). Whether there is any correlation between urocortin's neuroprotective effect and possible inhibition of cell cycling could be an area for further investigation.
References:
Muramatsu Y, Sugino N, Suzuki T, Totsune K, Takahashi K, Tashiro A, Hongo M, Oki Y, Sasano H. Urocortin and corticotropin-releasing factor receptor expression in normal cycling human ovaries. J Clin Endocrinol Metab. 2001 Mar;86(3):1362-9. PubMed.
Carlson KW, Nawy SS, Wei ET, Sadée W, Filov VA, Rezsova VV, Slominski A, Quillan JM. Inhibition of mouse melanoma cell proliferation by corticotropin-releasing hormone and its analogs. Anticancer Res. 2001 Mar-Apr;21(2A):1173-9. PubMed.
Muramatsu Y, Fukushima K, Iino K, Totsune K, Takahashi K, Suzuki T, Hirasawa G, Takeyama J, Ito M, Nose M, Tashiro A, Hongo M, Oki Y, Nagura H, Sasano H. Urocortin and corticotropin-releasing factor receptor expression in the human colonic mucosa. Peptides. 2000 Dec;21(12):1799-809. PubMed.
De Souza EB. Corticotropin-releasing factor receptors: physiology, pharmacology, biochemistry and role in central nervous system and immune disorders. Psychoneuroendocrinology. 1995;20(8):789-819. PubMed.
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