Parkinson's disease (PD) is a disorder that destroys neurons in the extrapyramidal dopaminergic pathway in the brain. In the world, the number of patients with PD is 10 million now and PD is a disease whose incidence increases with age. In particular, genetic and environmental factors are believed to cause PD. Rigidity in striated muscles, characteristic tremors, and posture disorder is specified as the main clinical symptoms of PD. Although radical treatment of PD is not possible today, some drugs that slow the progression of it and are effective in its symptoms are used successfully in the clinic. Among them, the essential drug is levodopa. However, an important disadvantage in the drug treatment of PD is that the beneficial effects of the drugs decrease over time in long-term use. Moreover, their use of them is associated with serious side effects. Therefore, it is important to develop new treatment strategies for the treatment of PD. When a great effort continues to discover new drugs having different action mechanisms, it is expected that developed nanotechnology-based drugs for PD therapy become important, additionally.
Olanow CW, Schapira AHV. Therapeutic prospects for Parkinson disease. Annals of Neurology (2013) 74(3):337–347.
Bandres-Ciga S, Diez-Fairen M, Kim JJ, Singleton AB. Genetics of Parkinson’s disease: An introspection of its journey towards precision medicine. Neurobiology of Disease (2020) 137:104782.
Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease. Nature Reviews Disease Primers (2017) 3(1):17013.
Heinzel S, Berg D, Gasser T, Chen H, Yao C, Postuma RB. Update of the MDS research criteria for prodromal Parkinson’s disease. Movement Disorders (2019) 34(10):1464–1470.
Beiske AG, Loge JH, Rønningen A, Svensson E. Pain in Parkinson’s disease: Prevalence and characteristics. Pain (2009) 141(1):173– 177.
Li J, Mi T-M, Zhu B, Ma J-H, Han C, Li Y, et al. High-frequency repetitive transcranial magnetic stimulation over the primary motor cortex relieves musculoskeletal pain in patients with Parkinson’s disease: A randomized controlled trial. Parkinsonism & Related Disorders (2020) 80:113–119.
Schrag A, Quinn N. Dyskinesias and motor fluctuations in Parkinson’s disease. Brain (2000) 123(11):2297–2305.
Muangpaisan W, Mathews A, Hori H, Seidel D. A systematic review of the worldwide prevalence and incidence of Parkinson’s disease. Journal of the Medical Association of Thailand = Chotmaihet thangphaet (2011) 94(6):749–755.
Roche VF, Zito SW, Lemke TL, Williams DA. Foye’s principles of medicinal chemistry:1626.
Corti O, Lesage S, Brice A. What Genetics Tells us About the Causes and Mechanisms of Parkinson’s Disease. Physiological Reviews (2011) 91(4):1161–1218.
Jankovic J. Current approaches to the treatment of Parkinson’s disease. Neuropsychiatric Disease and Treatment (2008):743.
Rajput AH, Birdi S. Epidemiology of Parkinson’s disease. Parkinsonism & Related Disorders (1997) 3(4):175–186.
Kurman Y. Parkinson Hastalığı ve İlişkili Olduğu Genler. Düzce Üniversitesi Bilim ve Teknoloji Dergisi (2018) 6(1):231–239.
Tysnes O-B, Storstein A. Epidemiology of Parkinson’s disease. Journal of Neural Transmission (2017) 124(8):901–905.
Lin C-H, Chen P-L, Tai C-H, Lin H-I, Chen C-S, Chen M-L, et al. A clinical and genetic study of early-onset and familial parkinsonism in taiwan: An integrated approach combining gene dosage analysis and next-generation sequencing. Movement Disorders (2019) 34(4):506–515.
Shan W, Li J, Xu W, Li H, Zuo Z. Critical role of UQCRC1 in embryo survival brain ischemic tolerance and normal cognition in mice. Cellular and molecular life sciences CMLS (2019) 76(7):1381–1396.
Hoffman GG, Lee S, Christiano AM, Chung-Honet LC, Cheng W, Katchman S, et al. Complete coding sequence intron/exon organization and chromosomal location of the gene for the core I protein of human ubiquinol-cytochrome c reductase. The Journal of biological chemistry (1993) 268(28):21113–21119.
McKnight S, Hack N. Toxin-Induced Parkinsonism. Neurologic Clinics (2020) 38(4):853–865.
Quinn LP, Crook B, Hows ME, Vidgeon-Hart M, Chapman H, Upton N, et al. The PPARγ agonist pioglitazone is effective in the MPTP mouse model of Parkinson’s disease through inhibition of monoamine oxidase B. British Journal of Pharmacology (2008) 154(1):226–233.
Clapp P, Bhave SV, Hoffman PL. How adaptation of the brain to alcohol leads to dependence: a pharmacological perspective. Alcohol research & health the journal of the National Institute on Alcohol Abuse and Alcoholism (2008) 31(4):310–339.
Guigoni C, Aubert I, Li Q, Gurevich VV, Benovic JL, Ferry S, et al. Pathogenesis of levodopa-induced dyskinesia: focus on D1 and D3 dopamine receptors. Parkinsonism & Related Disorders (2005) 11:S25–S29.
Moore TJ, Glenmullen J, Mattison DR. Reports of Pathological Gambling Hypersexuality and Compulsive Shopping Associated With Dopamine Receptor Agonist Drugs. JAMA Internal Medicine (2014) 174(12):1930.
Yang P, Perlmutter JS, Benzinger TL, Morris JC, Xu J. Dopamine D3 receptor: A neglected participant in Parkinson Disease pathogenesis and treatment? Ageing Research Reviews (2020) 57:100994.
Garau L, Govoni S, Stefanini E, Trabucchi M, Spano PF. Dopamine receptors: Pharmacological and anatomical evidences indicate that two distinct dopamine receptor populations are present in rat striatum. Life Sciences (1978) 23(17–18):1745–1750.
Surmeier DJ, Kitai ST. Chapter 20 D1 and D2 dopamine receptor modulation of sodium and potassium currents in rat neostriatal neurons. In: (1993). p. 309–324.
Lewis M, Huang X, Nichols D, Mailman R. D1 and Functionally Selective Dopamine Agonists as Neuroprotective Agents in Parkinsons Disease. CNS & Neurological Disorders - Drug Targets (2008) 5(3):345–353.
Einhorn LC, Oxford GS. Guanine nucleotide binding proteins mediate D2 dopamine receptor activation of a potassium channel in rat lactotrophs. The Journal of Physiology (1993) 462(1):563–578.
Shiraishi T, Nishikawa N, Mukai Y, Takahashi Y. High levodopa plasma concentration after oral administration predicts levodopainduced dyskinesia in Parkinson’s disease. Parkinsonism & Related Disorders (2020) 75:80–84.
Rodriguez-Oroz MC, López-Azcárate J, Garcia-Garcia D, Alegre M, Toledo J, Valencia M, et al. Involvement of the subthalamic nucleus in impulse control disorders associated with Parkinson’s disease. Brain (2011) 134(1):36–49.
Magyar K, Szende B. (-)-Deprenyl A Selective MAO-B Inhibitor with Apoptotic and Anti-apoptotic Properties. NeuroToxicology (2004) 25(1–2):233–242.
O’Brien EM, Tipton KF, Meroni M, Dostert P. Inhibition of monoamine oxidase by clorgyline analogues. In: Amine Oxidases: Function and Dysfunction. Vienna: Springer Vienna (1994). p. 295– 305.
Larit F, Elokely KM, Chaurasiya ND, Benyahia S, Nael MA, León F, et al. Inhibition of human monoamine oxidase A and B by flavonoids isolated from two Algerian medicinal plants. Phytomedicine (2018) 40:27–36.
Ulmanen I, Lundstrom K. Cell-free synthesis of rat and human catechol O-methyltransferase. Insertion of the membrane-bound form into microsomal membranes in vitro. European Journal of Biochemistry (1991) 202(3):1013–1020.
Tenhunen J, Salminen M, Lundstrom K, Kiviluoto T, Savolainen R, Ulmanen I. Genomic organization of the human catechol Omethyltransferase gene and its expression from two distinct promoters. European Journal of Biochemistry (1994) 223(3):1049– 1059.
Myöhänen TT, Schendzielorz N, Männistö PT. Distribution of catechol-O-methyltransferase (COMT) proteins and enzymatic activities in wild-type and soluble COMT deficient mice. Journal of Neurochemistry (2010):no-no.
Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S, et al. Functional Analysis of Genetic Variation in Catechol-OMethyltransferase (COMT): Effects on mRNA Protein and Enzyme Activity in Postmortem Human Brain. The American Journal of Human Genetics (2004) 75(5):807–821. 130 International Journal of Innovative Research and Reviews 6(2) 121-131
Du X, Schwander M, Moresco EMY, Viviani P, Haller C, Hildebrand MS, et al. A catechol-O-methyltransferase that is essential for auditory function in mice and humans. Proceedings of the National Academy of Sciences (2008) 105(38):14609–14614.
Hosák L. Role of the COMT gene Val158Met polymorphism in mental disorders: A review. European Psychiatry (2007) 22(5):276– 281.
Kambur O, Männistö PT. Catechol-O-Methyltransferase and Pain. In: (2010). p. 227–279.
Bonifácio MJ, Palma PN, Almeida L, Soares-da-Silva P. CatecholO-methyltransferase and Its Inhibitors in Parkinson’s Disease. CNS Drug Reviews (2007) 13(3):352–379.
Reches A, Fahn S. Catechol-O-methyltransferase and Parkinson’s disease. Advances in neurology (1984) 40:171–179.
Lotta T, Vidgren J, Tilgmann C, Ulmanen I, Melén K, Julkunen I, et al. Kinetics of human soluble and membrane-bound catechol Omethyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry (1995) 34(13):4202–4210.
Borgulya J, Da Prada M, Dingemanse J, Scherschlicht R, B. S, G. Z. CatecholO-methyltransferase (COMT) inhibitor. Drugs Future (1991) Ro 40-7592(16):719–721.
Backstrom R, Honkanen E, Pippuri A, Kairisalo P, Pystynen J, Heinola K, et al. Synthesis of some novel potent and selective catechol O-methyltransferase inhibitors. Journal of Medicinal Chemistry (1989) 32(4):841–846.
Kaakkola S, Gordin A, Männistö PT. General properties and clinical possibilities of new selective inhibitors of catechol Omethyltransferase. General Pharmacology: The Vascular System (1994) 25(5):813–824.
Borges N, Vieira-Coelho MA, Parada A, Soares-da-Silva P. Studies on the tight-binding nature of tolcapone inhibition of soluble and membrane-bound rat brain catechol-O-methyltransferase. The Journal of pharmacology and experimental therapeutics (1997) 282(2):812–817.
Almeida L, Soares-da-Silva P. Pharmacokinetics and Pharmacodynamics of BIA 3-202 a Novel COMT Inhibitor during First Administration to Humans. Drugs in R & D (2003) 4(4):207– 217.
Ferreira JJ, Almeida L, Cunha L, Ticmeanu M, Rosa MM, Januário C, et al. Effects of Nebicapone on Levodopa Pharmacokinetics Catechol-O-methyltransferase Activity and Motor Fluctuations in Patients with Parkinson Disease. Clinical Neuropharmacology (2008) 31(1):2–18.
Hamaue N, Ogata A, Terado M, Tsuchida S, Yabe I, Sasaki H, et al. Entacapone a catechol-O-methyltransferase inhibitor improves the motor activity and dopamine content of basal ganglia in a rat model of Parkinson’s disease induced by Japanese encephalitis virus. Brain Research (2010) 1309:110–115.
Grünig D, Felser A, Bouitbir J, Krähenbühl S. The catechol-Omethyltransferase inhibitors tolcapone and entacapone uncouple and inhibit the mitochondrial respiratory chain in HepaRG cells. Toxicology in Vitro (2017) 42:337–347.
Ebersbach G, Storch A. Tolcapone in elderly patients with Parkinson’s disease: A prospective open-label multicenter noninterventional trial. Archives of Gerontology and Geriatrics (2009) 49(1):e40–e44.
Calne DB, Leigh PN, Teychenne PF, Bamji AN, Greenacre JK. TREATMENT OF PARKINSONISM WITH BROMOCRIPTINE. The Lancet (1974) 304(7893):1355–1356.
Goetz CG, Poewe W, Rascol O, Sampaio C. Evidence-based medical review update: Pharmacological and surgical treatments of Parkinson’s disease: 2001 to 2004. Movement Disorders (2005) 20(5):523–539.
Ahlskog JE, Muenter MD. Pergolide: Long-Term Use in Parkinson’s Disease. Mayo Clinic Proceedings (1988) 63(10):979– 987.
Horowski R. A history of dopamine agonists. From the physiology and pharmacology of dopamine to therapies for prolactinomas and Parkinson’s disease – a subjective view. Journal of Neural Transmission (2007) 114(1):127–134.
Bonuccelli U, Del Dotto P, Rascol O. Role of dopamine receptor agonists in the treatment of early Parkinson’s disease. Parkinsonism & Related Disorders (2009) 15:S44–S53.
Cedarbaum JM. Clinical Pharmacokinetics of Anti-Parkinsonian Drugs. Clinical Pharmacokinetics (1987) 13(3):141–178.
Tan BK, Hutchinson JS. Blood pressure, plasma and pituitary prolactin responses to bromocriptine in New Zealand genetically hypertensive and normotensive rats. Clinical and experimental pharmacology & physiology (1989) 16(1):13–18.
Sánchez-Criado JE, van der Schoot P. Effect of bromocriptine and progesterone on the length of the ovarian cycle in 4- and 5-day estrous cyclic rats. Revista espanola de fisiologia (1989) 45(3):235– 238.
Friedman JH. Parkinson’s disease psychosis 2010: A review article. Parkinsonism & Related Disorders (2010) 16(9):553–560.
Bennett JP, Piercey MF. Pramipexole — a new dopamine agonist for the treatment of Parkinson’s disease. Journal of the Neurological Sciences (1999) 163(1):25–31.
Meric C, Pirdogan E, Gunday Toker O, Tekin A, Bakim B, Celik S. Depending on the use of pramipexole in Parkinson’s disease mania with psychotic features: a case report. Turkish Journal of Psychiatry (2013) 24.
Bhatia K, Brooks DJ, Burn DJ, Clarke CE, Playfer J, Sawle GV, et al. Guidelines for the management of Parkinson’s disease. The Parkinson’s Disease Consensus Working Group. Hospital medicine (London, England 1998) (1998) 59(6):469–480.
Eden RJ, Wallduck MS, Patel B, Owen DA. Autonomic and haemodynamic responses to SK&F 101468 (ropinirole) a DA2 agonist in anaesthetised cats. European Journal of Pharmacology (1990) 175(3):333–340.
Mey C, Enterling D, Meineke I, Yeulet S. Interactions between domperidone and ropinirole a novel dopamine D2- receptor agonist. British Journal of Clinical Pharmacology (1991) 32(4):483–488.
Eden RJ, Costall B, Domeney AM, Gerrard PA, Harvey CA, Kelly ME, et al. Preclinical pharmacology of ropinirole (SK&F 101468-A) a novel dopamine D2 agonist. Pharmacology Biochemistry and Behavior (1991) 38(1):147–154.
Sohya K, O’Hashi K, Kunugi H. Linking rotigotine Parkinson’s disease and brain-derived neurotrophic factor. In: Genetics, Neurology, Behavior, and Diet in Parkinson’s Disease: Elsevier (2020). p. 221–232.
Jenner P. An Overview of Adenosine A2A Receptor Antagonists in Parkinson’s Disease. In: (2014). p. 71–86.
Armentero MT, Pinna A, Ferré S, Lanciego JL, Müller CE, Franco R. Past present and future of A2A adenosine receptor antagonists in the therapy of Parkinson’s disease. Pharmacology & Therapeutics (2011) 132(3):280–299.
Klüter H, Vieregge P, Stolze H, Kirchner H. Defective production of interleukin-2 in patients with idiopathic Parkinson’s disease. Journal of the Neurological Sciences (1995) 133(1–2):134–139.
Wandinger KP, Hagenah JM, Klüter H, Rothermundt M, Peters M, Vieregge P. Effects of amantadine treatment on in vitro production of interleukin-2 in de-novo patients with idiopathic Parkinson’s disease. Journal of Neuroimmunology (1999) 98(2):214–220.
Clark C, Woodson MM, Winge VB, Nagasawa HT. The antiviral drug amantadine has a direct inhibitory effect on T-lymphocytes. Immunopharmacology (1989) 18(3):195–204.
Takahashi S, Tohgi H, Yonezawa H, Obara S, Yamazaki E. The effect of trihexyphenidyl an anticholinergic agent on regional cerebral blood flow and oxygen metabolism in patients with Parkinson’s disease. Journal of the Neurological Sciences (1999) 167(1):56–61.
Corea N. Benztropine. In: xPharm: The Comprehensive Pharmacology Reference: Elsevier (2007). p. 1–4.
Nishiyama K, Mizuno T, Sakuta M, Kurisaki H. Chronic dementia in Parkinson’s disease treated by anticholinergic agents. Neuropsychological and neuroradiological examination. Advances in neurology (1993) 60:479–483.
Sadeh M, Braham J, Modan M. Effects of Anticholinergic Drugs on Memory in Parkinson’s Disease. Archives of Neurology (1982) 39(10):666–667.
Krystal JH. Subanesthetic Effects of the Noncompetitive NMDA Antagonist Ketamine in Humans. Archives of General Psychiatry (1994) 51(3):199.
Zarnowski T, Kleinrok Z, Turski WA, Czuczwar SJ. The NMDA antagonist procyclidine but not ifenprodil enhances the protective efficacy of common antiepileptics against maximal electroshockinduced seizures in mice. Journal of Neural Transmission (1994) 97(1):1–12.
Olney J, Labruyere J, Wang G, Wozniak D, Price M, Sesma M. NMDA antagonist neurotoxicity: mechanism and prevention. Science (1991) 254(5037):1515–1518.
Timberlake WH, Schwab RS, England AC. Biperiden (Akineton) in Parkinsonism. Archives of Neurology (1961) 5(5):560–564.
Fleischhacker WW, Barnas C, Günther V, Meise U, Stuppäck C, Unterweger B. Mood-altering effects of biperiden in healthy volunteers. Journal of Affective Disorders (1987) 12(2):153–157.
Strang RR. Orphenadrine In The Treatment of Parkinson’s Disease. Current medicine and drugs (1964) 5(1):24–31. Küçükoğlu and Nadaroğlu / Parkinson's Disease, Therapy with Drugs and Nanotechnology 131
Bhushan B. Introduction to Nanotechnology. In: (2017). p. 1–19.
Nalci OB, Nadaroglu H, Genc S, Hacimuftuoglu A, Alayli A. The effects of MgS nanoparticles-Cisplatin-bio-conjugate on SH-SY5Y neuroblastoma cell line. Molecular Biology Reports (2020).
Chen C, Duan Z, Yuan Y, Li R, Pang L, Liang J, et al. Peptide-22 and Cyclic RGD Functionalized Liposomes for Glioma Targeting Drug Delivery Overcoming BBB and BBTB. ACS Applied Materials & Interfaces (2017) 9(7):5864–5873.
Ebrahimi AK, Barani M, Sheikhshoaie I. Fabrication of a new superparamagnetic metal-organic framework with core-shell nanocomposite structures: Characterization biocompatibility and drug release study. Materials Science and Engineering: C (2018) 92:349–355.
Ertugrul MS, Nadaroglu H, Nalci OB, Hacimuftuoglu A, Alayli A. Preparation of CoS nanoparticles-cisplatin bio-conjugates and investigation of their effects on SH-SY5Y neuroblastoma cell line. Cytotechnology (2020) 72(6):885–896.
Senthilkumar T, Zhou L, Gu Q, Liu L, Lv F, Wang S. Conjugated Polymer Nanoparticles with Appended Photo‐Responsive Units for Controlled Drug Delivery Release and Imaging. Angewandte Chemie International Edition (2018) 57(40):13114–13119.
Müller RH, Keck CM. Drug Delivery to the Brain – Realization by Novel Drug Carriers. Journal of Nanoscience and Nanotechnology (2004) 4(5):471–483.
Jayaraj RL, Chandramohan V, Namasivayam E. Nanomedicines for parkinson disease: Current status and future perspective. International Journal of Pharma and Bio Sciences (2013) 4(1):692– 704.
Kabanov AV, Vinogradov SV. Nanogels as Pharmaceutical Carriers: Finite Networks of Infinite Capabilities. Angewandte Chemie International Edition (2009) 48(30):5418–5429.
Bronich TK, Bontha S, Shlyakhtenko LS, Bromberg L, Alan Hatton T, Kabanov AV. Template-assisted synthesis of nanogels from Pluronic-modified poly(acrylic acid). Journal of Drug Targeting (2006) 14(6):357–366.
Vingradov S, Zeman A, Batrakova E, Kabanov A. Polyplex Nanogel formulations for drug delivery of cytotoxic nucleoside analogs. Journal of Controlled Release (2005) 107(1):143–157.
Raemdonck K, Demeester J, Smedt S de. Advanced nanogel engineering for drug delivery. Soft Matter (2009) 5(4):707–715.
Kreuter J, Shamenkov D, Petrov V, Ramge P, Cychutek K, KochBrandt C, et al. Apolipoprotein-mediated Transport of Nanoparticlebound Drugs Across the Blood-Brain Barrier. Journal of Drug Targeting (2002) 10(4):317–325.
Ghazy E, Rahdar A, Barani M, Kyzas GZ. Nanomaterials for Parkinson disease: Recent progress. Journal of Molecular Structure (2020):129698.
Hu K, Chen X, Chen W, Zhang L, Li J, Ye J, et al. Neuroprotective effect of gold nanoparticles composites in Parkinson’s disease model. Nanomedicine: Nanotechnology, Biology, and Medicine (2018) 14(4):1123–1136.
Gao G, Gong D, Zhang M, Sun T. Chiral Gold Nanoclusters: A New Near-Infrared Fluorescent Probe. Acta Chimica Sinica (2016) 74(4):363.
Xu W, Tan L, Yu J-T. The link between the SNCA gene and parkinsonism. Neurobiology of Aging (2015) 36(3):1505–1518.
Lasagna-Reeves C, Gonzalez-Romero D, Barria MA, Olmedo I, Clos A, Sadagopa Ramanujam VM, et al. Bioaccumulation and toxicity of gold nanoparticles after repeated administration in mice. Biochemical and Biophysical Research Communications (2010) 393(4):649–655.
Kim D, Yoo JM, Hwang H, Lee J, Lee SH, Yun SP, et al. Graphene quantum dots prevent α-synucleinopathy in Parkinson’s disease. Nature Nanotechnology (2018) 13(9):812–818.
Luk KC, Kehm V, Carroll J, Zhang B, O’Brien P, Trojanowski JQ, et al. Pathological -Synuclein Transmission Initiates Parkinson-like Neurodegeneration in Nontransgenic Mice. Science (2012) 338(6109):949–953.
Spillantini MG, Schmidt ML, Lee VM-Y, Trojanowski JQ, Jakes R, Goedert M. α-Synuclein in Lewy bodies. Nature (1997) 388(6645):839–840.
Hegazy MAE, Maklad HM, Abd Elmonsif DA, Elnozhy FY, Alqubiea MA, Alenezi FA, et al. The possible role of cerium oxide (CeO 2 ) nanoparticles in prevention of neurobehavioral and neurochemical changes in 6-hydroxydopamine-induced parkinsonian disease. Alexandria Journal of Medicine (2017) 53(4):351–360.
Ruotolo R, Giorgio G de, Minato I, Bianchi M, Bussolati O, Marmiroli N. Cerium Oxide Nanoparticles Rescue α-SynucleinInduced Toxicity in a Yeast Model of Parkinson’s Disease. Nanomaterials (2020) 10(2):235.
Heckert EG, Karakoti AS, Seal S, Self WT. The role of cerium redox state in the SOD mimetic activity of nanoceria. Biomaterials (2008) 29(18):2705–2709.
The authors keep the copyrights of the published materials with them, but the authors are aggee to give an exclusive license to the publisher that transfers all publishing and commercial exploitation rights to the publisher. The puslisher then shares the content published in this journal under CC BY-NC-ND license.