Nanobiotechnology in Parkinson’s Disease

  • Pablo Vicente Torres-Ortega
  • Iván Martínez-Valbuena
  • Gloria Martí-Andrés
  • Amira Sayed Hanafy
  • María Rosario Luquin
  • Elisa GarbayoEmail author
  • María José Blanco-PrietoEmail author


Parkinson’s disease (PD) is a complex neurodegenerative disorder. It is characterized by a combination of motor and nonmotor symptoms that gradually appear as consequence of the selective loss of dopaminergic neurons in the substantia nigra pars compacta and the presence of Lewy bodies and dystrophic neurites, two abnormal structures composed by misfolded α-synuclein. Recent evidences suggest that the toxicity caused by α-synuclein relies on its oligomerization, which precedes the formation of the large α-synuclein aggregates. Several important contributions have been made in the PD field during recent years. However, an early and accurate diagnosis, together with the availability of disease-modifying therapies, still represents a major unmet need. The emergence of nanotechnology has provided new systems like ultra-sensitive biosensors that are able to detect PD-related biomarkers in complex but more accessible biological fluids, and novel MRI agents for contrast enhancement in imaging applications. Nanotechnology could also revolutionize the PD therapeutic pipeline, which is currently focused on the relief of motor symptoms. To date, the efficacy of nanotechnology in PD treatment has been supported by a large number of preclinical studies that have encapsulated different drugs in a wide range of nanoscale delivery systems such as nanoparticles, liposomes, exosomes, and quantum dots. In this chapter, we provide an overview of recent advances in the application of nanomedicine to both the diagnosis and treatment of PD. The main challenges anticipated, future perspectives, and the possibility of transferring these studies to future clinical trials are also discussed.


Parkinson’s disease Nanotechnology Diagnosis Treatment α-synuclein Neuroprotective therapies 


  1. Abdel-Haq H (2019) Blood exosomes as a tool for monitoring treatment efficacy and progression of neurodegenerative diseases. Neural Regen Res 14:72–74. Scholar
  2. Agrawal M, Ajazuddin TDK, Saraf S, Saraf S, Antimisiaris SG, Mourtas S, Hammarlund-Udenaes M, Alexander A (2017) Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer’s disease. J Control Release 260:61–77. Scholar
  3. AlDakheel A, Kalia LV, Lang AE (2014) Pathogenesis-Targeted, Disease-Modifying Therapies in Parkinson Disease. Neurotherapeutics 11:6–23CrossRefGoogle Scholar
  4. Athauda D, Maclagan K, Skene SS, Bajwa-Joseph M, Letchford D, Chowdhury K, Hibbert S, Budnik N, Zampedri L, Dickson J, Li Y, Aviles-Olmos I, Warner TT, Limousin P, Lees AJ, Greig NH, Tebbs S, Foltynie T (2017) Exenatide once weekly versus placebo in Parkinson’s disease: a randomised, double-blind, placebo-controlled trial. Lancet 6736:1–12. Scholar
  5. Barker R (1991) Substance P and neurodegenerative disorders. A speculative review. Neuropeptides 20:73–78PubMedGoogle Scholar
  6. Berardelli A, Wenning GK, Antonini A, Berg D, Bloem BR, Bonifati V, Brooks D, Burn DJ, Colosimo C, Fanciulli A, Ferreira J, Gasser T, Grandas F, Kanovsky P, Kostic V, Kulisevsky J, Oertel W, Poewe W, Reese J-P, Relja M, Ruzicka E, Schrag A, Seppi K, Taba P, Vidailhet M (2013) EFNS/MDS-ES recommendations for the diagnosis of Parkinson’s disease. Eur J Neurol 20:16–34. Scholar
  7. Braak H, Del Tredici K, Rüb U, de Vos RA, Jansen Steur EN, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24:197–211. Scholar
  8. Broski SM, Hunt CH, Johnson GB, Morreale RF, Lowe VJ, Peller PJ (2014) Structural and Functional Imaging in Parkinsonian Syndromes. RadioGraphics 34:1273–1292. Scholar
  9. Brundin P, Dave KD, Kordower JH (2017) Therapeutic approaches to target alpha-synuclein pathology. Exp Neurol 298:225–235. Scholar
  10. Brundin P, Melki R (2017) Prying into the Prion Hypothesis for Parkinson’s Disease. J Neurosci 37:9808–9818. Scholar
  11. Cacciatore I, Ciulla M, Fornasari E, Marinelli L, Di Stefano A (2016) Solid lipid nanoparticles as a drug delivery system for the treatment of neurodegenerative diseases. Expert Opin Drug Deliv 13:1121–1131. Scholar
  12. Cao Z, Wu Y, Liu G, Jiang Y, Wang X, Wang Z, Feng T (2019) α-Synuclein in salivary extracellular vesicles as a potential biomarker of Parkinson’s disease. Neurosci Lett 696:114–120. Scholar
  13. Carrizzo A, Forte M, Damato A, Trimarco V, Salzano F, Bartolo M, Maciag A, Puca AA, Vecchione C (2013) Antioxidant effects of resveratrol in cardiovascular, cerebral and metabolic diseases. Food Chem Toxicol 61:215–226. Scholar
  14. Chen-Plotkin AS, Zetterberg H (2018) Updating Our Definitions of Parkinson’s Disease for a Molecular Age. J Parkinsons Dis 8:S53–S57. Scholar
  15. Chen T, Li C, Li Y, Yi X, Lee SMY, Zheng Y (2016) Oral delivery of a nanocrystal formulation of schisantherin a with improved bioavailability and brain delivery for the treatment of Parkinson’s disease. Mol Pharm 13:3864–3875. Scholar
  16. Cui Q, Li X, Zhu H (2016) Curcumin ameliorates dopaminergic neuronal oxidative damage via activation of the Akt/Nrf2 pathway. Mol Med Rep 13:1381–1388. Scholar
  17. da Rocha LG, Bonfanti Santos D, Colle D, Gasnhar Moreira EL, Daniel Prediger R, Farina M, Khalil NM, Mara Mainardes R (2015) Improved neuroprotective effects of resveratrol-loaded polysorbate 80-coated poly(lactide) nanoparticles in MPTP-induced Parkinsonism. Nanomedicine 10:1127–1138. Scholar
  18. El-Say KM, El-Sawy HS (2017) Polymeric nanoparticles: Promising platform for drug delivery. Int J Pharm 528:675–691. Scholar
  19. Elzoghby AO (2013) Gelatin-based nanoparticles as drug and gene delivery systems: Reviewing three decades of research. J Control Release 172:1075–1091. Scholar
  20. Emamzadeh FN, Surguchov A (2018) Parkinson’s disease: Biomarkers, treatment, and risk factors. Front Neurosci 12:1–14. Scholar
  21. Eslamboli A (2005) Assessment of GDNF in primate models of Parkinson’s disease: comparison with human studies. Rev Neurosci 16:303–310CrossRefGoogle Scholar
  22. Esteves M, Cristóvão AC, Saraiva T, Rocha SM, Baltazar G, Ferreira L, Bernardino L (2015) Retinoic acid-loaded polymeric nanoparticles induce neuroprotection in a mouse model for parkinson’s disease. Front Aging Neurosci 7:1–10. Scholar
  23. Freeman TB, Cicchetti F, Cisbani G, Maxan A, Planel E, Kordower JH (2017) Presence of tau pathology within foetal neural allografts in patients with Huntington’s and Parkinson’s disease. Brain 140:2982–2992. Scholar
  24. Gámez-Valero A, Beyer K, Borràs FE (2019) Extracellular vesicles, new actors in the search for biomarkers of dementias. Neurobiol Aging 74:15–20. Scholar
  25. Ganguly U, Chakrabarti SS, Kaur U, Mukherjee A, Chakrabarti S (2018) Alpha-synuclein, Proteotoxicity and Parkinson’s Disease: Search for Neuroprotective Therapy. Curr Neuropharmacol 16:1086–1097. Scholar
  26. Garbayo E, Ansorena E, Lana H, Carmona-Abellan M del M, Marcilla I, Lanciego JL, Luquin MR and Blanco-Prieto MJ (2016) Brain delivery of microencapsulated GDNF induces functional and structural recovery in parkinsonian monkeys. Biomaterials 110:11–23. doi: Scholar
  27. Garbayo E, Ansorena E, Lanciego JL, Blanco-Prieto MJ, Aymerich MS (2011) Long-term neuroprotection and neurorestoration by glial cell-derived neurotrophic factor microspheres for the treatment of Parkinson’s disease. Mov Disord 26:1943–1947. Scholar
  28. Garbayo E, Estella-Hermoso de Mendoza A, Blanco-Prieto MJ (2014) Diagnostic and therapeutic uses of nanomaterials in the brain. Curr Med Chem 21:4100–4131CrossRefGoogle Scholar
  29. Garbayo E, Montero-Menei CN, Ansorena E, Lanciego JL, Aymerich MS, Blanco-Prieto MJ (2009) Effective GDNF brain delivery using microspheres-A promising strategy for Parkinson’s disease. J Control Release 135:119–126. Scholar
  30. Gui Y, Liu H, Zhang L, Lv W, Hu X (2015) Altered microRNA profiles in cerebrospinal fluid exosome in Parkinson disease and Alzheimer disease. Oncotarget 6:37043–37053. Scholar
  31. Haney MJ, Klyachko NL, Zhao Y, Gupta R, Plotnikova EG, He Z, Patel T, Piroyan A, Sokolsky M, Kabanov AV, Batrakova EV (2015) Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release 207:18–30. Scholar
  32. He S, Yan X (2013) From Resveratrol to Its Derivatives: New Sources of Natural Antioxidant. Curr Med Chem 20:1005–1017. Scholar
  33. Heckert EG, Karakoti AS, Seal S, Self WT (2008) The role of cerium redox state in the SOD mimetic activity of nanoceria. Biomaterials 29:2705–2709. Scholar
  34. Hegazy MA, Maklad HM, Samy DM, Abdelmonsif DA, El Sabaa BM, Elnozahy FY (2017) Cerium oxide nanoparticles could ameliorate behavioral and neurochemical impairments in 6-hydroxydopamine induced Parkinson’s disease in rats. Neurochem Int 108:361–371. Scholar
  35. Hernando S, Herran E, Figueiro-Silva J, Pedraz JL, Igartua M, Carro E, Hernandez RM (2018) Intranasal administration of TAT-conjugated lipid nanocarriers loading GDNF for Parkinson’s disease. Mol Neurobiol 55:145–155. Scholar
  36. Herrán E, Requejo C, Ruiz-Ortega JA, Aristieta A, Igartua M, Bengoetxea H, Ugedo L, Pedraz JL, Lafuente JV, Hernández RM (2014) Increased antiparkinson efficacy of the combined administration of VEGF- and GDNF-loaded nanospheres in a partial lesion model of Parkinson’s disease. Int J Nanomedicine 9:2677–2687. Scholar
  37. Herrmann Y, Bujnicki T, Zafiu C, Kulawik A, Kühbach K, Peters L, Fabig J, Willbold J, Bannach O, Willbold D (2017) Nanoparticle standards for immuno-based quantitation of α-synuclein oligomers in diagnostics of Parkinson’s disease and other synucleinopathies. Clin Chim Acta 466:152–159. Scholar
  38. Hu K, Chen X, Chen W, Zhang L (2018) Neuroprotective effect of gold nanoparticles composites in Parkinson ’ s disease model. Nanomedicine Nanotechnology, Biol Med 14:1123–1136. Scholar
  39. Huang R, Ma H, Guo Y, Liu S, Kuang Y, Shao K, Li J, Liu Y, Han L, Huang S, An S, Ye L, Lou J, Jiang C (2013) Angiopep-conjugated nanoparticles for targeted long-term gene therapy of parkinson’s disease. Pharm Res 30:2549–2559. Scholar
  40. Izadpanah M, Seddigh A, Ebrahimi Barough S, Fazeli SAS, Ai J (2018) Potential of Extracellular Vesicles in Neurodegenerative Diseases: Diagnostic and Therapeutic Indications. J Mol Neurosci 66:172–179. Scholar
  41. Jankovic J (2008) Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 79:368–376. Scholar
  42. Jin F, Wu Q, Lu YF, Gong QH, Shi JS (2008) Neuroprotective effect of resveratrol on 6-OHDA-induced Parkinson’s disease in rats. Eur J Pharmacol 600:78–82. Scholar
  43. Kalia LV, Kalia SK, McLean PJ, Lozano AM, Lang AE (2013) α-synuclein oligomers and clinical implications for parkinson disease. Ann Neurol 73:155–169. Scholar
  44. Kalia LV, Lang AE (2015) Parkinson’s disease. Lancet 386:896–912. Scholar
  45. Kanazawa T, Akiyama F, Kakizaki S, Takashima Y, Seta Y (2013) Delivery of siRNA to the brain using a combination of nose-to-brain delivery and cell-penetrating peptide-modified nano-micelles. Biomaterials 34:9220–9226. Scholar
  46. Kaushik AC, Bharadwaj S, Kumar S, Wei DQ (2018) Nano-particle mediated inhibition of Parkinson’s disease using computational biology approach. Sci Rep 8:9169. Scholar
  47. Khatri DK, Juvekar AR (2016) Neuroprotective effect of curcumin as evinced by abrogation of rotenone-induced motor deficits, oxidative and mitochondrial dysfunctions in mouse model of Parkinson’s disease. Pharmacol Biochem Behav 150–151:39–47. Scholar
  48. Kim D, Yoo JM, Hwang H, Lee J, Lee SH, Yun SP, Park MJ, Lee MJ, Choi S, Kwon SH, Lee S, Kwon SH, Kim S, Park YJ, Kinoshita M, Lee YH, Shin S, Paik SR, Lee SJ, Lee S, Hong BH, Ko HS (2018) Graphene quantum dots prevent α-synucleinopathy in Parkinson’s disease. Nat Nanotechnol 13:812–818. Scholar
  49. Kim T, Hyeon T (2014) Applications of inorganic nanoparticles as therapeutic agents. Nanotechnology 25:012001. Scholar
  50. Kitamura Y, Kojima M, Kurosawa T, Sasaki R, Ichihara S, Hiraku Y, Tomimoto H, Murata M, Oikawa S (2018) Proteomic Profiling of Exosomal Proteins for Blood-based Biomarkers in Parkinson’s Disease. Neuroscience 392:121–128. Scholar
  51. Korsvik C, Patil S, Seal S and Self WT (2007) Superoxide dismutase mimetic properties exhibited by vacancy engineered ceria nanoparticles. Chem Commun 0:1056–1058. doi:
  52. Kouli A, Torsney KM, Kuan W (2018) Parkinson’s Disease: Pathogenesis and Clinical Aspects. Codon Publications, BrisbaneGoogle Scholar
  53. Kreuter J (2014) Drug delivery to the central nervous system by polymeric nanoparticles: What do we know? Adv Drug Deliv Rev 71:2–14. Scholar
  54. Kundu P, Das M, Tripathy K, Sahoo SK (2016) Delivery of Dual Drug Loaded Lipid Based Nanoparticles across the Blood-Brain Barrier Impart Enhanced Neuroprotection in a Rotenone Induced Mouse Model of Parkinson’s Disease. ACS Chem Neurosci 7:1658–1670. Scholar
  55. Lang AE, Gill S, Patel NK, Lozano A, Nutt JG, Penn R, Brooks DJ, Hotton G, Moro E, Heywood P, Brodsky MA, Burchiel K, Kelly P, Dalvi A, Scott B, Stacy M, Turner D, Wooten VGF, Elias WJ, Laws ER, Dhawan V, Stoessl AJ, Matcham J, Coffey RJ, Traub M (2006) Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease. Ann Neurol 59:459–466. Scholar
  56. Li X, Zhao X, Xu X, Mao X, Liu Z, Li H, Guo L, Bi K, Jia Y (2014) Schisantherin A recovers Aβ-induced neurodegeneration with cognitive decline in mice. Physiol Behav 132:10–16. Scholar
  57. Li Y, Perry T, Kindy MS, Harvey BK, Tweedie D, Holloway HW, Powers K, Shen H, Egan JM, Sambamurti K, Brossi A, Lahiri DK, Mattson MP, Hoffer BJ, Wang Y, Greig NH (2009) GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism. Proc Natl Acad Sci 106:1285–1290. Scholar
  58. Lim PK, Patel SA, Gregory LA, Rameshwar P (2010) Neurogenesis: Role for microRNAs and Mesenchymal Stem Cells in Pathological States. Curr Med Chem 17:2159–2167. Scholar
  59. Lin CY, Hsieh HY, Chen CM, Wu SR, Tsai CH, Huang CY, Hua MY, Wei KC, Yeh CK, Liu HL (2016) Non-invasive, neuron-specific gene therapy by focused ultrasound-induced blood-brain barrier opening in Parkinson’s disease mouse model. J Control Release 235:72–81. Scholar
  60. Lin Y-L, Chang H-C, Chen T-L, Chang J-H, Chiu W-T, Lin J-W, Chen R-M (2010) Resveratrol Protects against Oxidized LDL-Induced Breakage of the Blood-Brain Barrier by Lessening Disruption of Tight Junctions and Apoptotic Insults to Mouse Cerebrovascular Endothelial Cells. J Nutr 140:2187–2192. Scholar
  61. Liu XG, Lu S, Liu DQ, Zhang L, Zhang LX, Yu XL, Liu RT (2019) ScFv-conjugated superparamagnetic iron oxide nanoparticles for MRI-based diagnosis in transgenic mouse models of Parkinson’s and Huntington’s diseases. Brain Res 1707:141–153. Scholar
  62. Lonskaya I, Hebron ML, Desforges NM, Schachter JB, Moussa CE-H (2014) Nilotinib-induced autophagic changes increase endogenous parkin level and ubiquitination, leading to amyloid clearance. J Mol Med 92:373–386. Scholar
  63. Lu K-T, Ko M-C, Chen B-Y, Huang J-C, Hsieh C-W, Lee M-C, Chiou RYY, Wung B-S, Peng C-H, Yang Y-L (2008) Neuroprotective Effects of Resveratrol on MPTP-Induced Neuron Loss Mediated by Free Radical Scavenging. J Agric Food Chem 56:6910–6913. Scholar
  64. Maden M (2007) Retinoic acid in the development, regeneration and maintenance of the nervous system. Nat Rev Neurosci 8:755–765. Scholar
  65. Mavridis IN, Meliou M, Pyrgelis ES, Agapiou E (2018) Nanotechnology and Parkinson’s disease. In: Design of nanostructures for versatile therapeutic applications. Elsevier, New York, pp 1–29Google Scholar
  66. Mead BP, Kim N, Miller GW, Hodges D, Mastorakos P, Klibanov AL, Mandell JW, Hirsh J, Suk JS, Hanes J, Price RJ (2017) Novel Focused Ultrasound Gene Therapy Approach Noninvasively Restores Dopaminergic Neuron Function in a Rat Parkinson’s Disease Model. Nano Lett 17:3533–3542. Scholar
  67. Migliore MM, Ortiz R, Dye S, Campbell RB, Amiji MM, Waszczak BL (2014) Neurotrophic and neuroprotective efficacy of intranasal GDNF in a rat model of Parkinson’s disease. Neuroscience 274:11–23. Scholar
  68. Molaei MJ (2019) A review on nanostructured carbon quantum dots and their applications in biotechnology, sensors, and chemiluminescence. Talanta 196:456–478. Scholar
  69. Munchau A, Bhatia KP (2000) Pharmacological treatment of Parkinson’s disease. Postgrad. Med. J. 76:602–610CrossRefGoogle Scholar
  70. Nair R, Kumar KSA, Priya KV, Sevukarajan M (2011) Recent advances in solid lipid nanoparticle based drug delivery systems. J Biomed Sci Res 3:368–384Google Scholar
  71. Nitta SK, Numata K (2013) Biopolymer-based nanoparticles for drug/gene delivery and tissue engineering. Int J Mol Sci 14:1629–1654. Scholar
  72. Niu J, Xie J, Guo K, Zhang X, Xia F, Zhao X, Song L, Zhuge D, Li X, Zhao Y, Huang Z (2018) Efficient treatment of Parkinson’s disease using ultrasonography-guided rhFGF20 proteoliposomes. Drug Deliv 25:1560–1569. Scholar
  73. Niu S, Zhang LK, Zhang L, Zhuang S, Zhan X, Chen WY, Du S, Yin L, You R, Li CH, Guan YQ (2017) Inhibition by multifunctional magnetic nanoparticles loaded with alpha-synuclein RNAi plasmid in a Parkinson’s disease model. Theranostics 7:344–356. Scholar
  74. Nussbaum RL, Ellis CE (2003) Alzheimer’s Disease and Parkinson’s Disease. N Engl J Med 348:1356–1364. Scholar
  75. Nutt JG, Burchiel KJ, Comella CL, Jankovic J, Lang AE, Laws ER, Lozano AM, Penn RD, Simpson RK, Stacy M, Wooten GF, ICV GDNF Study Group, Implanted intracerebroventricular. Glial cell line-derived neurotrophic factor (2003) Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD. Neurology 60:69–73CrossRefGoogle Scholar
  76. Obeso JA, Stamelou M, Goetz CG, Poewe W, Lang AE, Weintraub D, Burn D, Halliday GM, Bezard E, Przedborski S, Lehericy S, Brooks DJ, Rothwell JC, Hallett M, DeLong MR, Marras C, Tanner CM, Ross GW, Langston JW, Klein C, Bonifati V, Jankovic J, Lozano AM, Deuschl G, Bergman H, Tolosa E, Rodriguez-Violante M, Fahn S, Postuma RB, Berg D, Marek K, Standaert DG, Surmeier DJ, Olanow CW, Kordower JH, Calabresi P, Schapira AHV, Stoessl AJ (2017) Past, present, and future of Parkinson’s disease: A special essay on the 200th Anniversary of the Shaking Palsy. Mov Disord 32:1264–1310. Scholar
  77. Ohmichi T, Mitsuhashi M, Tatebe H, Kasai T, Ali El-Agnaf OM, Tokuda T (2018) Quantification of brain-derived extracellular vesicles in plasma as a biomarker to diagnose Parkinson’s and related diseases. Parkinsonism Relat Disord. Scholar
  78. Olanow CW (1993) A radical hypothesis for neurodegeneration. Trends Neurosci 16:439–444. Scholar
  79. Pagan F, Hebron M, Valadez EH, Torres-Yaghi Y, Huang X, Mills RR, Wilmarth BM, Howard H, Dunn C, Carlson A, Lawler A, Rogers SL, Falconer RA, Ahn J, Li Z, Moussa C (2016) Nilotinib Effects in Parkinson’s disease and Dementia with Lewy bodies. J Parkinsons Dis 6:503–517. Scholar
  80. Pal A, Singh A, Nag TC, Chattopadhyay P, Mathur R, Jain S (2013) Iron oxide nanoparticles and magnetic field exposure promote functional recovery by attenuating free radical-induced damage in rats with spinal cord transection. Int J Nanomedicine 8:2259–2272. Scholar
  81. Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, Schrag A-E, Lang AE (2017) Parkinson disease. Nat Rev Dis Prim 3:17013. Scholar
  82. Postuma RB, Berg D, Stern M, Poewe W, Olanow CW, Oertel W, Obeso J, Marek K, Litvan I, Lang AE, Halliday G, Goetz CG, Gasser T, Dubois B, Chan P, Bloem BR, Adler CH, Deuschl G (2015) MDS clinical diagnostic criteria for Parkinson’s disease. Mov Disord 30:1591–1601. Scholar
  83. Qin Y, Chen H, Zhang Q, Wang X, Yuan W, Kuai R, Tang J, Zhang L, Zhang Z, Zhang Q, Liu J, He Q (2011) Liposome formulated with TAT-modified cholesterol for improving brain delivery and therapeutic efficacy on brain glioma in animals. Int J Pharm 420:304–312. Scholar
  84. Rege SD, Geetha T, Griffin GD, Broderick TL, Babu JR (2014) Neuroprotective effects of resveratrol in Alzheimer disease pathology. Front Aging Neurosci 6:218. Scholar
  85. Rizzo G, Copetti M, Arcuti S, Martino D, Fontana A, Logroscino G (2016) Accuracy of clinical diagnosis of Parkinson disease. Neurology 86:566–576. Scholar
  86. Rodríguez-Nogales C, Garbayo E, Martínez-Valbuena I, Sebastián V, Luquin MR, Blanco-Prieto MJ (2016) Development and characterization of polo-like kinase 2 loaded nanoparticles-A novel strategy for (serine-129) phosphorylation of alpha-synuclein. Int J Pharm 514:142–149. Scholar
  87. Ross C, Taylor M, Fullwood N, Allsop D (2018) Liposome delivery systems for the treatment of Alzheimer’s disease. Int J Nanomedicine 13:8507–8522. Scholar
  88. Santos T, Ferreira R, Maia J, Agasse F, Xapelli S, Cortes L, Bragança J, Malva JO, Ferreira L, Bernardino L (2012) Polymeric Nanoparticles to Control the Differentiation of Neural Stem Cells in the Subventricular Zone of the Brain. ACS Nano 6:10463–10474. Scholar
  89. Saraiva C, Paiva J, Santos T, Ferreira L, Bernardino L (2016) MicroRNA-124 loaded nanoparticles enhance brain repair in Parkinson’s disease. J Control Release 235:291–305. Scholar
  90. Schenk DB, Koller M, Ness DK, Griffith SG, Grundman M, Zago W, Soto J, Atiee G, Ostrowitzki S, Kinney GG (2017) First-in-human assessment of PRX002, an anti-α-synuclein monoclonal antibody, in healthy volunteers. Mov Disord 32:211–218. Scholar
  91. Shen Q, Temple S (2009) Fine control: microRNA regulation of adult neurogenesis. Nat Neurosci 12:369–370. Scholar
  92. Singleton A, Hardy J (2016) The Evolution of Genetics: Alzheimer’s and Parkinson’s Diseases. Neuron 90:1154–1163. Scholar
  93. Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388:839–840. Scholar
  94. Taheri RA, Akhtari Y, Tohidi Moghadam T, Ranjbar B (2018) Assembly of gold nanorods on HSA amyloid fibrils to develop a conductive nanoscaffold for potential biomedical and biosensing applications. Sci Rep 8:9333. Scholar
  95. Tang CC, Poston KL, Eckert T, Feigin A, Frucht S, Gudesblatt M, Dhawan V, Lesser M, Vonsattel J-P, Fahn S, Eidelberg D (2010) Differential diagnosis of parkinsonism: a metabolic imaging study using pattern analysis. Lancet Neurol 9:149–158. Scholar
  96. Tapeinos C, Battaglini M, Ciofani G (2017) Advances in the design of solid lipid nanoparticles and nanostructured lipid carriers for targeting brain diseases. J Control Release 264:306–332. Scholar
  97. Thakur P, Breger LS, Lundblad M, Wan OW, Mattsson B, Luk KC, Lee VMY, Trojanowski JQ, Björklund A (2017) Modeling Parkinson’s disease pathology by combination of fibril seeds and α-synuclein overexpression in the rat brain. Proc Natl Acad Sci U S A 114:E8284–E8293. Scholar
  98. Thenganatt MA, Jankovic J (2014) Parkinson Disease Subtypes. JAMA Neurol 71:499. Scholar
  99. Timbie KF, Mead BP, Price RJ (2015) Drug and gene delivery across the blood-brain barrier with focused ultrasound. J Control Release 219:61–75. Scholar
  100. Tiwari MN, Agarwal S, Bhatnagar P, Singhal NK, Tiwari SK, Kumar P, Chauhan LKS, Patel DK, Chaturvedi RK, Singh MP, Gupta KC (2013) Nicotine-encapsulated poly(lactic-co-glycolic) acid nanoparticles improve neuroprotective efficacy against MPTP-induced parkinsonism. Free Radic Biol Med 65:704–718. Scholar
  101. Tome D, Fonseca C, Campos F, Baltazar G (2017) Role of Neurotrophic Factors in Parkinson’s Disease. Curr Pharm Des 23:809–838. Scholar
  102. Torres-Ortega PV, Saludas L, Hanafy AS, Garbayo E, Blanco-Prieto MJ (2019) Micro- and nanotechnology approaches to improve Parkinson’s disease therapy. J Control Release 295:201–213. Scholar
  103. Umarao P, Bose S, Bhattacharyya S, Kumar A, Jain S (2016) Neuroprotective Potential of Superparamagnetic Iron Oxide Nanoparticles Along with Exposure to Electromagnetic Field in 6-OHDA Rat Model of Parkinson’s Disease. J Nanosci Nanotechnol 16:261–269. Scholar
  104. Vivero-Escoto JL, Huang YT (2011) Inorganic-organic hybrid nanomaterials for therapeutic and diagnostic imaging applications. Int J Mol Sci 12:3888–3927. Scholar
  105. Wang N, Jin X, Guo D, Tong G, Zhu X (2017) Iron Chelation Nanoparticles with Delayed Saturation as an Effective Therapy for Parkinson Disease. Biomacromolecules 18:461–474. Scholar
  106. Whone AL, Boca M, Luz M, Woolley M, Mooney L, Dharia S, Broadfoot J, Cronin D, Schroers C, Barua NU, Longpre L, Barclay CL, Boiko C, Johnson GA, Fibiger HC, Harrison R, Lewis O, Pritchard G, Howell M, Irving C, Johnson D, Kinch S, Marshall C, Lawrence AD, Blinder S, Sossi V, Stoessl AJ, Skinner P, Mohr E, Gill SS (2019) Extended Treatment with Glial Cell Line-Derived Neurotrophic Factor in Parkinson’s Disease. J Parkinsons Dis 78:1–13. Scholar
  107. Wood MJ, Simons JP, Schapira AHV, Wiklander PBO, Al-Shawi R, Nordin JZ, El-Andaloussi S, Vithlani M, Alvarez-Erviti L, Cooper JM (2014) Systemic exosomal siRNA delivery reduced alpha-synuclein aggregates in brains of transgenic mice. Mov Disord 29:1476–1485. Scholar
  108. Wu X, Zheng T, Zhang B (2017) Exosomes in Parkinson’s Disease. Neurosci. Bull. 33:331–338CrossRefGoogle Scholar
  109. Xu Z, Arbizu J and Pavese N (2018) PET molecular imaging in atypical parkinsonism. In: International review of neurobiology, 1st edn. Elsevier Inc., pp 3–36Google Scholar
  110. Yang P, Zhu J, Huang Y, Zhang X, Lei P, Bush AI, Xiang Q, Su Z, Zhang Q (2016a) Human Basic Fibroblast Growth Factor Inhibits Tau Phosphorylation via the PI3K/Akt-GSK3β Signaling Pathway in a 6-Hydroxydopamine-Induced Model of Parkinson’s Disease. Neurodegener Dis 16:357–369. Scholar
  111. Yang S-Y, Chiu M-J, Lin C-H, Horng H-E, Yang C-C, Chieh J-J, Chen H-H, Liu B-H (2016b) Development of an ultra-high sensitive immunoassay with plasma biomarker for differentiating Parkinson disease dementia from Parkinson disease using antibody functionalized magnetic nanoparticles. J Nanobiotechnology 14:41. Scholar
  112. Yasuhara T, Shingo T, Muraoka K, Kameda M, Agari T, Wen Ji Y, Hayase H, Hamada H, Borlongan CV, Date I (2005) Neurorescue effects of VEGF on a rat model of Parkinson’s disease. Brain Res 1053:10–18. Scholar
  113. Yue P, Gao L, Wang X, Ding X, Teng J (2018a) Ultrasound-triggered effects of the microbubbles coupled to GDNF- and Nurr1-loaded PEGylated liposomes in a rat model of Parkinson’s disease. J Cell Biochem 119:4581–4591. Scholar
  114. Yue P, Miao W, Gao L, Zhao X, Teng J (2018b) Ultrasound-triggered effects of the microbubbles coupled to GDNF plasmid-loaded PEGylated liposomes in a rat model of Parkinson’s disease. Front Neurosci 12:222. Scholar
  115. Yurek D, Hasselrot U, Sesenoglu-Laird O, Padegimas L, Cooper M (2017) Intracerebral injections of DNA nanoparticles encoding for a therapeutic gene provide partial neuroprotection in an animal model of neurodegeneration. Nanomedicine Nanotechnology, Biol Med 13:2209–2217. Scholar
  116. Zahoor I, Shafi A, Haq E (2018) Pharmacological Treatment of Parkinson’s Disease. Codon Publications.
  117. Zhang X, Gao F, Wang D, Li C, Fu Y, He W, Zhang J (2018) Tau pathology in Parkinson’s disease. Front Neurol 9:809. Scholar
  118. Zhao YZ, Jin RR, Yang W, Xiang Q, Yu WZ, Lin Q, Tian FR, Mao KL, Lv CZ, Wáng YXJ, Lu CT (2016) Using gelatin nanoparticle mediated intranasal delivery of neuropeptide substance P to enhance neuro-recovery in hemiparkinsonian rats. PLoS One 11:1–18. Scholar
  119. Zhao YZ, Li X, Lu CT, Lin M, Chen LJ, Xiang Q, Zhang M, Jin RR, Jiang X, Shen XT, Li XK, Cai J (2014) Gelatin nanostructured lipid carriers-mediated intranasal delivery of basic fibroblast growth factor enhances functional recovery in hemiparkinsonian rats. Nanomedicine Nanotechnology, Biol Med 10:755–764. Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Pablo Vicente Torres-Ortega
    • 1
  • Iván Martínez-Valbuena
    • 2
    • 3
  • Gloria Martí-Andrés
    • 2
    • 3
  • Amira Sayed Hanafy
    • 4
    • 5
  • María Rosario Luquin
    • 2
    • 3
  • Elisa Garbayo
    • 1
    • 3
    Email author
  • María José Blanco-Prieto
    • 1
    • 3
    Email author
  1. 1.Department of Pharmaceutical Technology and Chemistry, Faculty of Pharmacy and NutritionUniversidad de NavarraPamplonaSpain
  2. 2.Department of Neurology and NeurosciencesCentro de Investigación Médica Aplicada and Clínica Universidad de NavarraPamplonaSpain
  3. 3.Instituto de Investigación Sanitaria de Navarra, IdiSNAPamplonaSpain
  4. 4.Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy and Drug ManufacturingPharos University in Alexandria (PUA)AlexandriaEgypt
  5. 5.Department of PharmacyLudwig-Maximilians-Universität MünchenMunichGermany

Personalised recommendations