And neurodegenerative diseases

Endogenous estrogens are known to be active in a number of areas of the brain. There are indications that estrogens may play a role in mood, locomotor activity, pain sensitivity, vulnerability to neurodegenerative diseases and cognition (McEwan, 1999). In humans, the blood brain barrier is not fiilly developed at birth and, for this reason, the central nervous system (CNS) may be more sensitive to phytoestrogens in utero or at birth. As ERs are expressed in the CNS, phytoestrogens may also be active in this area. 

Excitable membranes maintain and rapidly modulate substantial transmembrane ion gradients in response to stimuli 576 Specific lipid messengers are cleaved from reservoir phospholipids by phospholipases upon activation by various stimuli 576 Phospholipids in synaptic membranes are an important target in seizures, head injury, neurodegenerative diseases and cerebral ischemia 576 Some molecular species of phospholipids in excitable membranes are reservoirs of bioactive lipids that act as messengers 576 Mammalian phospholipids generally contain polyunsaturated fatty acyl chains almost exclusively esterified to the second carbon of glycerol 577... 

Curtis, M.A., Eriksson, P.S., Faull, R.L. (2007b) Progenitor cells and adult neurogenesis in neurodegenerative diseases and injuries of the basal ganglia. Clin Exp Pharmacol Physiol 34, 528-32. 

In every disease in which an abnormal protein is found there must be pathways of processing the protein to generate its functional form and pathways for degradation. These pathways are being investi gated for all of the neurodegenerative diseases and none more intensively than for Alzheimer disease. 

Lipid peroxidation is one of the major sources of free-radical mediated injury that directly damages membranes and generates a number of secondary products. In particular, markers of lipid peroxidation have been found to be elevated in brain tissues and body fluids in several neurodegenerative diseases, and the role of lipid peroxidation has been extensively discussed in the context of their pathogenesis. Peroxidation of membrane lipids can have numerous effects, including increased membrane rigidity, decreased activity of membrane-bound enzymes (e.g., sodium pumps), altered activity of membrane receptors, and altered permeability [Anzai et al., 1999 Yehuda et al., 2002], In addition to effects on phospholipids, lipid-initiated radicals can also directly attack membrane proteins and induce lipid-lipid, lipid-protein, and protein-protein cross-linking, all of which obviously have effects on membrane function. 

Emerit J., Edeas M., and Bricaire F. (2004). Neurodegenerative diseases and oxidative stress. Biomed. Pharmacother. 58 39-46. 

Kwak S., and Weiss J.H. 2006 Calcium-permeable AMPA channels in neurodegenerative disease and ischemia. Curr Opin Neurobiol 16, 281-287. 

PAOLO Ciana Center of Excellence on Neurodegenerative Diseases and Department of Pharmacological Sciences University of Milan, Milan, Italy... 

NE is mainly synthesized in the neurons of the locus coeruleus (LC), but also in the lateral tegmental field. In this review, we focus on the LC because of its implication in neurodegenerative diseases and cognition (Friedman et al., 1999). 

Li, J., Su, J., Li, W., Liu, W., Altura, B.T., and Altura, B.M. 2003. Peroxynitrite induces apoptosis in canine cerebral vascular muscle cells possible relation to neurodegenerative diseases and strokes. Neurosci Lett 350 173-177. 

In 1987, however, a study by Busto et al. (5) showed that small decreases in brain temperature (as little as 2-5°C below normal brain temperature) conferred a marked protective effect against experimental global cerebral ischemia. This finding, as well as subsequent animal studies that modeled neurodegenerative diseases and CNS injury, led to a resurgence of interest in mild hypothermia as a method of cerebral protection. 

Campbell, A. Inflammation, neurodegenerative diseases and environmental exposures. Ann. NY Acad. Sci. 1035, 117-132, 2004. 

Oxamyl dipeptides, (II), prepared by Karanewsky (4) were effective as ICE inhibitors of cysteine proteases and used in the treatment of inflammatory, autoimmune, and neurodegenerative diseases and for the prevention of ischemic injury. 

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