Neuronal cell protection

Femtomol levels of detection limits were also achieved in the determination of stimulant amines with the benzofurazan derivative 4-(Af,Af-dimethylaminosul-phonyl)-7-fluoro-2,l,3-benzoxadizole (DBD-F) [73], DBD-F was successfully applied to the PO-CL detection of amino acids and epinephrine [74] and a P-blocker, metoprolol [75], 4-(Af,Af-Dimethylaminosulphonyl)-7-hydrazino-2,l,3-benzoxadizole (DBD-H) has also been used for PO-CL determination of a neuronal cell protective compound, propentofylline. The method was applied for the first time to determine propentofylline concentration in the dialysate obtained from the rat hippocampus [85],... 

C (81) isolated from Streptomyces sp. 833 [75-77] as neuronal cell protecting substances. The stereochemistry of these compounds remains to be established. 

Murakami Y, Kato S, Nakajima M, Matsuoka M, Kawai H, Shin-Ya K, Seto H (1996) Formobactin, a Novel Free Radical Scavenging and Neuron Cell Protecting Substance from Nocardia sp. J Antibiotics 49 839... 

I. -D. (1997). Neuronal cell protection activity of macrolactin A produced by Actinomadura sp. 

Naphthomycinol (68), produced by Streptomyces sp. PF7, was isolated as a novel neuronal cell protecting substance. Naphthomycinol (68) is the first compound reported which has a hydroxyl function at C-11 [106]. 

Kim and co-workers in another 1997 report described the characterization of mescengricin, 6, a novel neuronal cell protecting substance produced by Strep-tomyces griseoftavus. A combination of HMBC and D-HMBC experiments were used in the structure elucidation process. Correlations were observed in the D-HMBC spectrum to link the H-3 resonance to the C-IO quaternary carbon via three-bonds and to the C-11 and C-14 quaternary carbons via four-bonds in the -lactone portion of the molecule. The H-3 resonance was also linked via four-bonds to the C9a quaternary carbon. The indole NH proton at the 9-position of the or-carboline nucleus was linked in the D-HMBC to the C4b, C8a, and C9a quaternary carbons the last of these correlations across four-bonds the H-5 resonance was correlated to the C4a quaternary carbon via four-bonds. These authors also used the D-HMBC experiment to establish the long-range H- N correlations in the molecule (see following subsection). 

There are multiple mechanisms known to underlie the neuronal cell damage associated with injury or disease that at least theoretically could be targeted for pharmaceutical intervention. Currently however, there is no clinically available therapeutic agent that can reliably protect the brain from progressive neurodegenerative processes for sustained periods. Due to the extensive amount of preclinical research that has been conducted in recent years, there is a basis for optimism, however, it appears likely that some of these approaches will result in clinically effective therapeutic modalities in the near future. A short overview of some of the investigational approaches to combat neurodegeneration appears below. 

Kaul M, Ma Q, Medders KE, Desai MK, Lipton SA (2007) HIV-1 coieceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection. Cell Death Differ 14 296-305... 

Jung H, Toth PT, White PA, Miller RJ (2008) Monocyte chemoattractant protein-1 functions as a neuromodulator in dorsal root ganglia neurons. J Neurochem 104 254-263 Kahn L, Alonso G, Normand E, Manzoni OJ (2005) Repeated morphine treatment alters polysia-lylated neural cell adhesion molecule, glutamate decarboxylase-67 expression and ceU proliferation in the adult rat hippocampus. Em J Nemosci 21 493-500 Kaul M, Ma Q, Medders KE, Desai MK, Lipton SA (2007) HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection. Cell Death Differ (2) 296-305... 

The antioxidant property of ferulic acid and related compounds from rice bran was reported by Kikuzaki et al, (2002). Their results indicated that these compounds elicit their antioxidant function through radical scavenging activity and their affinity with lipid substrates. Another recent study reported by Butterfield et al, (2002) demonstrated that ferulic acid offers antioxidant protection against hydroxyl and peroxyl radical oxidation in synaptosomal and neuronal cell culture systems in vitro. The effect of ferulic acid on blood pressure (BP) was investigated in spontaneously hypertensive rats (SHR). After oral administration of ferulic acid the systolic blood pressure (SBP) decreased in a dose-dependent manner. There was a significant correlation between plasma ferulic acid and changes in the SBP of the tail artery, suggesting... 

BUTTERFIELD D A, MARINA A, JAROSLAW K, ANTONIO s (2002) FeruUc add antioxidant protection against hydroxyl and peroxyl radical oxidation in synaptosomal and neuronal cell culture systems in vitro Structure activity studies. JNutri Biochem, 13(5) 273-81. 

Kim DO, Heo HJ, Kim YJ, Yang HS and Lee CY. 2005. Sweet and sour cherry phenolics and their protective effects on neuronal cells. J Agric Food Chem 53(26) 9921-9927. 

Another amino acid taurine (Figure 29.21) is an effective scavenger of hypochlorous acid, which is known to participate in tissue damage associated with reperfusion injury mediated by neutrophils. Thus, taurine protected against the cytotoxic action of HOC1 in neuronal cells... 

The suggestion that eNOS-derived NO is implicated in neuronal cell death mechanisms in thiamine deficiency contrasts with current views in cerebral ischemia in which increased eNOS-derived NO is thought to play a neuro-protective role by virtue of its vasodilatory potential. 

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