Amyloid diseases, treatment

Bieschke J (2013) Natural compounds may open new routes to treatment of amyloid diseases. Neurotherapeutics 10 429-439... 

Major Applications Display device,5.6 photoresists, lithographic plates,. toner,io paints,n coating materials, 12 hair dye,i3 treatment of mechanical allodynia, regulation of cell proliferation,i5 diagnostic agents for diseases related with amyloid accumulation, treatment of virus infectious diseases, detecting enzyme activity, dental bleaching materialsi ... 

Evans KC, Berger EP, Cho CG, Weisgraber KH, Lansbury PT Jr. Apolipoprotein E is a kinetic but not a thermodynamic of amyloid formation implications for the pathogenesis and treatment of Alzheimer disease. Proc Natl Acad Sci USA 1995 92 763-767. 

Alzheimer s Disease This disease is due to the accumulation of j8-amyloid protein in the brain. The protein is believed to trigger brain degeneration through cell death of the neurons. Alzheimer s disease is characterized by loss of memory and intellectual performance, and slowness in thought. In the United States, a class of drugs called cholinesterase inhibitors is approved to treat Alzheimer s disease. Both Europe and the United States have approved a drug called memantine for treatment of Alzheimer s disease. 

Fig. 10.9 Pathogenic factors acting on neuronal targets in Alzheimer s disease and the process of pharmacological treatment. ABP, amyloid 3-protein APP, ABP precursor protein CHO, choies-teroi NFT-Tau, neurofibriiiary tangie tau...

Rockenstein, E., Mante, M., Alford, M., et al. (2005) High P-secretase activity elicits neurodegeneration in transgenic mice despite reductions in amyloid-P levels. Implications for the treatment of Alzheimer s disease. J. Biol. Chem., 280, 32957-32967. 

Soto, C. (1999) Amyloid disrupting drugs. Potential in the treatment of Alzheimer s disease. CNS Drugs, 12,347-356. 

Cherny, R.A. (2001) Treatment with a copper-zinc chelator markedly and rapidly inhibits P-amyloid accumulation in Alzheimer s disease transgenic mice. Neuron, 30, 665-676. 

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. 

X-Protein. Amyloid p i 42 peptide and r-protein have a clinical significance as early diagnostic markers in Alzheimer s disease (AD), and its evaluation is mandatory for efficient treatment. The mean levels of A/3i 42 and r-protein in CSF were significantly reduced (with high specificity and sensitivity) in patients in comparison to normal findings (M6). 

For obvious reasons of structural analogy to heparinoids the focus of this review is on sulfated carbohydrate derivatives. While it is not in all cases clear that these compounds really mimic the physiological activity of heparinoids, it is even less so for non-carbohydrate sulfates or sulfonates. Examples of the latter class include suramin and the simple 1,3-propanediol disulfate. Suramin is a sulfonat-ed bis-naphthalene derivative used as a drug to treat African trypanosomiasis and onchocerciasis (a filarial infection) it was also tested in a number of other indications including adrenocortical carcinomas and AIDS. A wider use is, however, restricted by various toxic effects [66]. 1,3-Propanediol disulfate reduced inflammation-associated amyloid progression in vivo after oral administration which may be relevant to the treatment of Alzheimer s disease [67]. 

Coppen A, Ghose K, Montgomery S, et al Continuation therapy with amitriptyline in depression. Br J Psychiatry 133 28-33, 1978 Coppen A, Swade C, Wood K Lithium restores abnormal platelet 5-HT transport in patients with affective disorders. Br J Psychiatry 136 235-238, 1980 Coppen A, Swade C, Jones SA, et al Depression and tetrahydrobiopterin the folate connection. J Affect Disord 16 103-107, 1989 Cordell B 3-Amyloid formation as a potential therapeutic target for Alzheimer s disease. Annu Rev Pharmacol Toxicol 34 69-89, 1994 Corkin S Acetylcholine, aging, and Alzheimer s disease imphcations of treatment. Trends Neurosci 4 287-290, 1981... 

Golden RN, Morris JE, Sack DA Combined lithium-tricyclic treatment of obsessive-compulsive disorder. Biol Psychiatry 23 181-185, 1988 Goldenberg G, Lang W, Podreka 1, et al Are cognitive deficits in Parkinson s disease caused by frontal lobe dysfunction Journal of Psychophysiology 4 137-144, 1990 Goldgaber D, Harris HW, Hla T Interleukin-1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells. Proc Natl Acad Sci U S A 86 7606-7610, 1989... 

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