Frontiers in Alzheimer's Disease Therapeutics

Overview

Journal Ther Adv Chronic Dis

Publisher Sage Publications

Date 2011 Jul 12

PMID 21743833

Citations 12

Authors

Jeremy G Stone

Gemma Casadesus

Kasia Gustaw-Rothenberg

Sandra L Siedlak

Xinglong Wang

Xiongwei Zhu

George Perry

Rudy J Castellani

Mark A Smith

Affiliations

Soon will be listed here.

Abstract

Alzheimer disease (AD) is a progressive neurodegenerative disease which begins with insidious deterioration of higher cognition and progresses to severe dementia. Clinical symptoms typically involve impairment of memory and at least one other cognitive domain. Because of the exponential increase in the incidence of AD with age, the aging population across the world has seen a congruous increase AD, emphasizing the importance of disease altering therapy. Current therapeutics on the market, including cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists, provide symptomatic relief but do not alter progression of the disease. Therefore, progress in the areas of prevention and disease modification may be of critical interest. In this review, we summarize novel AD therapeutics that are currently being explored, and also mechanisms of action of specific drugs within the context of current knowledge of AD pathologic pathways.

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References

Bowen R, Isley J, Atkinson R . An association of elevated serum gonadotropin concentrations and Alzheimer disease?. J Neuroendocrinol. 2000; 12(4):351-4. DOI: 10.1046/j.1365-2826.2000.00461.x. View

Bachurin S, Shevtsova E, Kireeva E, Oxenkrug G, Sablin S . Mitochondria as a target for neurotoxins and neuroprotective agents. Ann N Y Acad Sci. 2003; 993:334-44; discussion 345-9. DOI: 10.1111/j.1749-6632.2003.tb07541.x. View

Liu G, Men P, Kudo W, Perry G, Smith M . Nanoparticle-chelator conjugates as inhibitors of amyloid-beta aggregation and neurotoxicity: a novel therapeutic approach for Alzheimer disease. Neurosci Lett. 2009; 455(3):187-90. PMC: 2683427. DOI: 10.1016/j.neulet.2009.03.064. View

Liu F, Iqbal K, Grundke-Iqbal I, Hart G, Gong C . O-GlcNAcylation regulates phosphorylation of tau: a mechanism involved in Alzheimer's disease. Proc Natl Acad Sci U S A. 2004; 101(29):10804-9. PMC: 490015. DOI: 10.1073/pnas.0400348101. View

Hampel H, Ewers M, Burger K, Annas P, Mortberg A, Bogstedt A . Lithium trial in Alzheimer's disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study. J Clin Psychiatry. 2009; 70(6):922-31. View

Corrada M, Kawas C, Hallfrisch J, Muller D, Brookmeyer R . Reduced risk of Alzheimer's disease with high folate intake: the Baltimore Longitudinal Study of Aging. Alzheimers Dement. 2009; 1(1):11-8. PMC: 3375831. DOI: 10.1016/j.jalz.2005.06.001. View

Wong G, Manfra D, Poulet F, Zhang Q, Josien H, Bara T . Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J Biol Chem. 2004; 279(13):12876-82. DOI: 10.1074/jbc.M311652200. View

Sano M, Ernesto C, Thomas R, Klauber M, Schafer K, Grundman M . A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N Engl J Med. 1997; 336(17):1216-22. DOI: 10.1056/NEJM199704243361704. View

Parks J, Smith T, Trimmer P, Bennett Jr J, Parker Jr W . Neurotoxic Abeta peptides increase oxidative stress in vivo through NMDA-receptor and nitric-oxide-synthase mechanisms, and inhibit complex IV activity and induce a mitochondrial permeability transition in vitro. J Neurochem. 2001; 76(4):1050-6. DOI: 10.1046/j.1471-4159.2001.00112.x. View

10.

Lee J, Boo J, Ryu H . The failure of mitochondria leads to neurodegeneration: Do mitochondria need a jump start?. Adv Drug Deliv Rev. 2009; 61(14):1316-23. PMC: 2783929. DOI: 10.1016/j.addr.2009.07.016. View

11.

Wadsworth T, Bishop J, Pappu A, Woltjer R, Quinn J . Evaluation of coenzyme Q as an antioxidant strategy for Alzheimer's disease. J Alzheimers Dis. 2008; 14(2):225-34. PMC: 2931577. DOI: 10.3233/jad-2008-14210. View

12.

Nunomura A, Tamaoki T, Tanaka K, Motohashi N, Nakamura M, Hayashi T . Intraneuronal amyloid beta accumulation and oxidative damage to nucleic acids in Alzheimer disease. Neurobiol Dis. 2009; 37(3):731-7. PMC: 2825655. DOI: 10.1016/j.nbd.2009.12.012. View

13.

Brunden K, Trojanowski J, Lee V . Advances in tau-focused drug discovery for Alzheimer's disease and related tauopathies. Nat Rev Drug Discov. 2009; 8(10):783-93. PMC: 2787232. DOI: 10.1038/nrd2959. View

14.

Perrig W, Perrig P, Stahelin H . The relation between antioxidants and memory performance in the old and very old. J Am Geriatr Soc. 1997; 45(6):718-24. DOI: 10.1111/j.1532-5415.1997.tb01476.x. View

15.

Kontush A . Alzheimer's amyloid-beta as a preventive antioxidant for brain lipoproteins. Cell Mol Neurobiol. 2002; 21(4):299-315. PMC: 11533814. DOI: 10.1023/a:1012629603390. View

16.

Griffin W, Sheng J, Roberts G, Mrak R . Interleukin-1 expression in different plaque types in Alzheimer's disease: significance in plaque evolution. J Neuropathol Exp Neurol. 1995; 54(2):276-81. DOI: 10.1097/00005072-199503000-00014. View

17.

Cornelius C, Fastbom J, Winblad B, Viitanen M . Aspirin, NSAIDs, risk of dementia, and influence of the apolipoprotein E epsilon 4 allele in an elderly population. Neuroepidemiology. 2004; 23(3):135-43. DOI: 10.1159/000075957. View

18.

Crowe A, Huang W, Ballatore C, Johnson R, Hogan A, Huang R . Identification of aminothienopyridazine inhibitors of tau assembly by quantitative high-throughput screening. Biochemistry. 2009; 48(32):7732-45. PMC: 2773749. DOI: 10.1021/bi9006435. View

19.

Bonda D, Bajic V, Spremo-Potparevic B, Casadesus G, Zhu X, Smith M . Review: cell cycle aberrations and neurodegeneration. Neuropathol Appl Neurobiol. 2010; 36(2):157-63. PMC: 5907796. DOI: 10.1111/j.1365-2990.2010.01064.x. View

20.

Poeggeler B, Miravalle L, Zagorski M, Wisniewski T, Chyan Y, Zhang Y . Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the Alzheimer amyloid Abeta peptide. Biochemistry. 2001; 40(49):14995-5001. DOI: 10.1021/bi0114269. View