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Current Neuropharmacology

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ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

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Review Article

Alzheimer’s Disease – Future Therapy Based on Dendrimers

Author(s): Gjumrakch Aliev*, Ghulam Md Ashraf , Vadim V. Tarasov, Vladimir N. Chubarev, Jerzy Leszek, Kazimierz Gasiorowski, Alfiya Makhmutovа, Saleh Salem Baeesa, Marco Avila-Rodriguez, Aleksey A. Ustyugov and Sergey O. Bachurin

Volume 17, Issue 3, 2019

Page: [288 - 294] Pages: 7

DOI: 10.2174/1570159X16666180918164623

Price: $65

Abstract

Alzheimer’s disease (AD) is characterized by the loss of neurons. It is the most common cause of dementia in the elderly population accompanied by pathological degeneration of neurofibrillary tangles. Senile plaques are formed with beta-amyloid, hyperphosphoryled tau protein, apolipoprotein E and presenilin associated with protease activity [amyloid beta (Aβ), gamma-secretase (γS)]. The molecular mechanisms of neurodegeneration include apoptosis, oxidative stress (free radical generation), inflammation, immune activation, and others. The lack of effective treatments for AD stems mainly from the incomplete understanding the causes of AD. Currently, there are several hypotheses explaining the early mechanisms of AD pathogenesis. Recent years witnessed an unprecedented research growth in the area of nanotechnology, which uses atomic, molecular and macromolecular methods to create products in microscale (nanoscale) dimensions. In this article, we have discussed the role of nanotechnology in the development and improvement of techniques for early diagnosis and effective treatment of AD. Since AD pathology is practically irreversible, applications of disease-modifying treatments could be successful only if early diagnosis of AD is available. This review highlights various possibilities for the early diagnosis and therapy of AD and investigates potential adaptation of nanoparticles-dendrimers as a class of well-defined branched polymers that are chemically synthesized with a well-defined shape, size and nanoscopic physicochemical properties reminiscent of the proteins for the treatment of neurodegenerative diseases.

Keywords: Alzheimer's disease, dendrimers, molecular neurodegeneration, nanoparticles-dendrimers, protein misfolding, treatment strategies.

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[1]
Modi G, Pillay V, Choonara YE, Ndesendo VM, du Toit LC, Naidoo D. Nanotechnological applications for the treatment of neurodegenerative disorders. Prog Neurobiol 2009; 88(4): 272-85.
[http://dx.doi.org/10.1016/j.pneurobio.2009.05.002] [PMID: 19486920]
[2]
Astruc D, Boisselier E, Ornelas C. Dendrimers designed for functions: from physical, photophysical, and supramolecular properties to applications in sensing, catalysis, molecular electronics, photonics, and nanomedicine. Chem Rev 2010; 110(4): 1857-959.
[http://dx.doi.org/10.1021/cr900327d] [PMID: 20356105]
[3]
Tomalia DA, Baker H, Dewald J, et al. A new class of polymers: starburst-dendritic macromolecules. Polym J 1985; 17: 117.
[http://dx.doi.org/10.1295/polymj.17.117]
[4]
Buhleier E, Wehner W, Vögtle F. “cascade”- and “nonskid-chain-like” syntheses of molecular cavity topologies. Synthesis 1978; 1978(02): 155-8.
[http://dx.doi.org/10.1055/s-1978-24702]
[5]
Newkome GR, Yao Z, Baker GR, Gupta VK. Micelles. Part 1. Cascade molecules: a new approach to micelles. A [27]-arborol. J Org Chem 1985; 50(11): 2003-4.
[http://dx.doi.org/10. 1021/jo00211a052]
[6]
Tomalia DA, Baker H, Dewald J, et al. Dendritic macromolecules: synthesis of starburst dendrimers. Macromolecules 1986; 19(9): 2466-8.
[http://dx.doi.org/10.1021/ma00163a029]
[7]
Holister P, Vas CR, Harper T. Dendrimers. Technol White Papers 2003; 6: 1-15.
[8]
Caminati G, Turro NJ, Tomalia DA. Photophysical investigation of starburst dendrimers and their interactions with anionic and cationic surfactants. Am Chem Soc 1990; 112(23): 8515-22.
[http://dx.doi.org/10.1021/ja00179a041]
[9]
Nanjwade BK, Bechra HM, Derkar GK, Manvi FV, Nanjwade VK. Dendrimers: emerging polymers for drug-delivery systems. Eur J Pharm Sci 2009; 38(3): 185-96.
[http://dx.doi.org/dx.doi. org/10.1016/j.ejps.2009.07.008] [PMID: 19646528]
[10]
Maciejewski M. 1982.
[11]
Malik N, Evagorou EG, Duncan R. Dendrimer-platinate: a novel approach to cancer chemotherapy. Anticancer Drugs 1999; 10(8): 767-76.
[http://dx.doi.org/10.1097/00001813-199909000-00010] [PMID: 10573209]
[12]
Svenson S, Tomalia DA. Dendrimers in biomedical applications--reflections on the field. Adv Drug Deliv Rev 2005; 57(15): 2106-29.
[http://dx.doi.org/10.1016/j.addr.2005.09.018] [PMID: 16305813]
[13]
Esfand R, Tomalia DA. Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications. Drug Discov Today 2001; 6(8): 427-36.
[http://dx.doi.org/ 10.1016/S1359-6446(01)01757-3] [PMID: 11301287]
[14]
Zhu S, Hong M, Zhang L, Tang G, Jiang Y, Pei Y. PEGylated PAMAM dendrimer-doxorubicin conjugates: in vitro evaluation and in vivo tumor accumulation. Pharm Res 2010; 27(1): 161-74.
[http://dx.doi.org/10.1007/s11095-009-9992-1] [PMID: 19862607]
[15]
Sato N, Kobayashi H, Saga T, et al. Tumor targeting and imaging of intraperitoneal tumors by use of antisense oligo-DNA complexed with dendrimers and/or avidin in mice. Clin Cancer Res 2001; 7(11): 3606-12.
[PMID: 11705883]
[16]
Pavan GM, Posocco P, Tagliabue A, et al. PAMAM dendrimers for siRNA delivery: computational and experimental insights. Chemistry 2010; 16(26): 7781-95.
[http://dx.doi.org/10.1002/chem.200903258] [PMID: 20496352]
[17]
Wiener EC, Brechbiel MW, Brothers H, et al. Dendrimer-based metal chelates: a new class of magnetic resonance imaging contrast agents. Magn Reson Med 1994; 31(1): 1-8.
[http://dx.doi.org/10. 1002/mrm.1910310102] [PMID: 8121264]
[18]
Balogh L, Bielinska A, Eichman J, et al. Dendrimer nanocomposites in medicine 2002.
[19]
Bourne N, Stanberry LR, Kern ER, Holan G, Matthews B, Bernstein DI. Dendrimers, a new class of candidate topical microbicides with activity against herpes simplex virus infection. Antimicrob Agents Chemother 2000; 44(9): 2471-4.
[http://dx.doi.org/dx.doi. org/10.1128/AAC.44.9.2471-2474.2000] [PMID: 10952597]
[20]
Jevprasesphant R, Penny J, Jalal R, Attwood D, McKeown NB, D’Emanuele A. The influence of surface modification on the cytotoxicity of PAMAM dendrimers. Int J Pharm 2003; 252(1-2): 263-6.
[http://dx.doi.org/10.1016/S0378-5173(02)00623-3] [PMID: 12550802]
[21]
Glenner GG, Wong CW. Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 1984; 120(3): 885-90.
[http://dx.doi.org/10.1016/S0006-291X(84)80190-4] [PMID: 6375662]
[22]
Goedert M, Spillantini MG, Cairns NJ, Crowther RA. Tau proteins of Alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms. Neuron 1992; 8(1): 159-68.
[http://dx.doi.org/10.1016/0896-6273(92)90117-V] [PMID: 1530909]
[23]
Dobryszycka W, Gąsiorowski K, Leszek J. 2004.
[24]
Mattson MP. Oxidative stress, perturbed calcium homeostasis, and immune dysfunction in Alzheimer’s disease. J Neurovirol 2002; 8(6): 539-50.
[http://dx.doi.org/10.1080/13550280290100978] [PMID: 12476348]
[25]
Blach-Olszewska Z, Zaczynska E, Gustaw-Rothenberg K, et al. The innate immunity in Alzheimer disease- relevance to Pathogenesis and Therapy. Curr Pharm Des 2015; 21(25): 3582-8.
[http://dx.doi.org/dx. doi.org/10.2174/1381612821666150710144829] [PMID: 26166611]
[26]
Bojarski L, Herms J, Kuznicki J. Calcium dysregulation in Alzheimer’s disease. Neurochem Int 2008; 52(4-5): 621-33.
[http://dx.doi.org/10.1016/j.neuint.2007.10.002] [PMID: 18035450]
[27]
Vetulani J, Leszek J. Neurochemia zaburzeń procesów poznawczych 2011.
[28]
Benseny-Cases N, Klementieva O, Malý J, Cladera J. Granular non-fibrillar aggregates and toxicity in Alzheimer’s disease. Curr Alzheimer Res 2012; 9(8): 962-71.
[http://dx.doi.org/10.2174/156720512803251129] [PMID: 22272608]
[29]
Lorenzo A, Yankner BA. Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red. Proc Natl Acad Sci USA 1994; 91(25): 12243-7.
[http://dx.doi.org/10.1073/pnas.91.25.12243] [PMID: 7991613]
[30]
Klajnert B, Cortijo-Arellano M, Cladera J, Bryszewska M. Influence of dendrimer’s structure on its activity against amyloid fibril formation. Biochem Biophys Res Commun 2006; 345(1): 21-8.
[http://dx.doi.org/10.1016/j.bbrc.2006.04.041] [PMID: 16674918]
[31]
Klajnert B, Wasiak T, Ionov M, et al. Dendrimers reduce toxicity of Aβ 1-28 peptide during aggregation and accelerate fibril formation. Nanomedicine (Lond) 2012; 8(8): 1372-8.
[http://dx.doi.org/10.1016/j.nano.2012.03.005] [PMID: 22465497]
[32]
Klementieva O, Benseny-Cases N, Gella A, Appelhans D, Voit B, Cladera J. Dense shell glycodendrimers as potential nontoxic anti-amyloidogenic agents in Alzheimer’s disease. Amyloid-dendrimer aggregates morphology and cell toxicity. Biomacromolecules 2011; 12(11): 3903-9.
[http://dx.doi.org/10.1021/bm2008636] [PMID: 21936579]
[33]
Wasiak T, Marcinkowska M, Pieszynski I, et al. Cationic phosphorus dendrimers and therapy for Alzheimer’s disease. New J Chem 2015; 39(6): 4852-9.
[http://dx.doi.org/10.1039/C5NJ00309A]
[34]
Lee VM, Goedert M, Trojanowski JQ. Neurodegenerative tauopathies. Annu Rev Neurosci 2001; 24: 1121-59.
[http://dx.doi.org/dx. doi.org/10.1146/annurev.neuro.24.1.1121] [PMID: 11520930]
[35]
Forman MS, Trojanowski JQ, Lee VM. Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs. Nat Med 2004; 10(10): 1055-63.
[http://dx.doi.org/dx. doi.org/10.1038/nm1113] [PMID: 15459709]
[36]
Ballatore C, Lee VM, Trojanowski JQ. Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat Rev Neurosci 2007; 8(9): 663-72.
[http://dx.doi.org/10.1038/nrn2194] [PMID: 17684513]
[37]
Wasiak T, Ionov M, Nieznanski K, et al. Phosphorus dendrimers affect Alzheimer’s (Aβ1-28) peptide and MAP-Tau protein aggregation. Mol Pharm 2012; 9(3): 458-69.
[http://dx.doi.org/10.1021/mp2005627] [PMID: 22206488]
[38]
Schachter AS, Davis KL. Alzheimer’s Disease. Curr Treat Options Neurol 2000; 2(1): 51-60.
[http://dx.doi.org/10.1007/s11940-000-0023-0] [PMID: 11096736]
[39]
Bruunsgaard H, Pedersen M, Pedersen BK. Aging and proinflammatory cytokines. Curr Opin Hematol 2001; 8(3): 131-6.
[http://dx.doi.org/10.1097/00062752-200105000-00001] [PMID: 11303144]
[40]
Dhanikula RS, Hildgen P. Synthesis and evaluation of novel dendrimers with a hydrophilic interior as nanocarriers for drug delivery. Bioconjug Chem 2006; 17(1): 29-41.
[http://dx.doi.org/ 10.1021/bc050184c] [PMID: 16417249]

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