APP inhibition

Cetraria ericetorum Eumarprotocetraric acid Depsidones APP Inhibition of HIV-1 reverse Pengsuparp... 

Usnea longissima) Lichesterinic Aliphatic and cycloali- APP Inhibition Epstein-Barr Y amamoto... 

Flavocetraria nivalis Flavocetraria cucullata Usnic acid Dibenzoftiranes APP Inhibition of tyrosine phosphatase Cytotoxic activity Apoptosis Antibiotic activity Antibacterial activity Antitrypanosomal activity Antiviral activity Francolini et al. (2004) De Carvahlo et ah (2005) Mayer et al. (2005) Elo et al. (2007) Fazio et al. (2007) Bazin et al. (2008) Burlando et al. (2009)... 

Lobaria linita Tenuiorin Depsides APP Inhibition of 5-lipoxygenase activity Ingolfsdottir and Gudmundsdottir (2002)... 

Parmelia nepalensis Protolichesterinic acid Aliphatic and APP Inhibition of Kumar and Muller... 

Stereocaulon azoreum Lobaric acid Depsidones APP Inhibition of et al. (1996)... 

Stereocaulon sasakii Stereocalpin A Didepsipeptide APP Inhibition of platelet-type et al. (2004)... 

Creitz, E.C., Inhibition of diffusion flames by methyl bromide and trifluoromethy 1-bromide applied to the fuel and oxygen sides of the reaction zone, J. Res. App. Phys. Chem., 65, 389, 1961. 

Our inhibitor design strategy was based on the premise that structural modifications in the base of purine riboside that enhance purine base hydration without impairing the binding of the hydrated species to the ADA binding site would result in purine riboside (PR) analogues with high ADA inhibitory potency. Since the apparent inhibition constant (Kj (app)) is related to the hydration equilibrium constant (Keq) and the inhibitory constant for the hydrated molecule (Kj ) by... 

Recent studies have examined the separation of APP and Notch processing effects in vivo. Dibenzazepinone 29 (LY-411,575) demonstrates significant reductions in plasma, CSF, and brain A (3 in transgenic mice [80-83]. Several toxicities attributed to inhibition of Notch processing, including effects on the intestine, thymus, and spleen, have also been characterized. Doses associated with partial inhibition of cortical A (340 levels by 29 in mice did not cause intestinal changes... 

Plots devised by Dixon to determine K, for tight-binding inhibitors, (a) A primary plot of v versus total inhibitor present ([/Id yields a concave line. In this example, [S] = 3 x Km and thus v = 67% of Straight lines drawn from Vo (when [/It = 0) through points corresponding to Vq/2, Vq/3, etc. intersect with the x-axis at points separated by a distance /Cj app/ when inhibition is competitive. When inhibition is noncompetitive, intersection points are separated by a distance equivalent to K. The positions of lines for n = 1 and n = 0 can then be deduced and the total enzyme concentration, [EJt, can be determined from the distance between the origin and the intersection point of the n = 0 line on the x-axis. If inhibition is competitive, this experiment is repeated at several different substrate concentrations such that a value for K, app is obtained at each substrate concentration. (b) Values for app are replotted versus [S], and the y-intercept yields a value for /Cj. If inhibition is noncompetitive, this replot is not necessary (see text)... 

Proteasome inhibition by lactacystin and Bz-LLL-COCHO (benzol-Leu-Leu-Leu-glyoxal) causes a significant increase of ABP and cell death by altering APP processing at the y-secretase site (406). Resveratrol does not inhibit ABP production because it has no effect on 3-, or y-secretases, but promotes instead intracellular degradation of ABP via a mechanism that involves the proteasome. The resveratrol-induced decrease of ABP can be effectively prevented by several selective proteasome inhibitors and by small interfering RNA-directed silencing on the proteasome subunit P5 (407). 

Espeseth, A.S., Xu, M., Huand, Q., et al. (2005) Compounds that bind APP and inhibit AP processing in vitro suggest a novel approach to Alzheimer disease therapeutics. J. Biol. Chem., 280, 17792-17797. 

Currently the only specific pharmacological therapeutic option available for AD patients is treatment with cholinesterase inhibitors, which provide moderate benefits in a subset of patients for a limited period [7]. More efficient future therapeutic strategies may be directed at the metabolic events resulting in Ap accumulation, for example by inhibition of P- or y-sec-retase [7], or at the prevention of neuronal loss by neurotrophin therapy [6]. The availability of transgenic mouse models of the disease, such as mice overexpressing APP mutants [8], and the utilization of primate models of cerebral amyloid [9] permits preclinical testing of novel diagnostic and therapeutic approaches. 

The protease [APP secretase) responsible for the normal cleavage of APP through the PA4 segment is unknown, but a number of proteases, including calpain [D. H. Small et al. 1992), a serine protease, and cathepsin B [Cataldo et al. 1991), have been proposed. It remains to be determined whether therapy should be directed at enhancing the function of the secretase to accelerate the breakdown of the PA4 segment or at inhibiting the enzyme to reduce APP turnover. 

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