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CNS & Neurological Disorders - Drug Targets


ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Review Article

Overview of Therapeutic Drugs and Methods for the Treatment of Parkinson’s Disease

Author(s): Andrew Schneider, Adam T. Sari, Hasan Alhaddad and Youssef Sari*

Volume 19 , Issue 3 , 2020

Page: [195 - 206] Pages: 12

DOI: 10.2174/1871527319666200525011110

Price: $65


Parkinson’s Disease (PD) is a neurodegenerative disease involving degeneration of dopaminergic neurons of the nigrostriatal pathways. Over the past decades, most of the medications for the treatment of PD patients have been used to modulate dopamine concentrations in the basal ganglia. This includes levodopa and its inhibitory metabolizing enzymes. In addition to modulating dopamine concentrations in the brain, there are D2-like dopamine receptor agonists that mimic the action of dopamine to compensate for the deficit in dopamine found in PD patients. Muscarinic antagonists’ drugs are used rarely due to some side effects. Monoamine oxidase inhibitors are among the first in line, and are considered popular drugs that reduce the metabolism of dopamine in PD patients. Furthermore, we discussed in this review the existence of certain glutamate receptor antagonists for the treatment of PD. Alternatively, we further discussed the potential therapeutic role of adenosine (2A) receptor antagonists, such as tozadenant and istradefylline in the treatment of PD. We also discussed the important role of serotonin1A receptor agonist, adrenergic autoreceptors (α2) antagonists and calcium channel blockers in the treatment of PD. Finally, neurotrophic factors, such as glial cell line-derived neurotrophic growth factor and brain-derived neurotrophic factor are considered the primary factors for neuroprotection in PD.

Keywords: Dopamine, MAO-B, glutamate, BDNF, GDNF, Parkinson's Disease (PD).

Graphical Abstract
DeMaagd G, Philip A. Parkinson’s disease and its management: part 1: disease entity, risk factors, pathophysiology, clinical presentation, and diagnosis. P&T 2015; 40(8): 504-32.
[PMID: 26236139]
Armstrong MJ, Okun MS. Diagnosis and treatment of Parkinson’s disease: a review. JAMA 2020; 323(6): 548-60.
[] [PMID: 32044947]
Athulya RT, Jayakrishnan S, Iype T, Rajan R, Alapatt PJ. Predictors of levo-dopa induced dyskinesias in Parkinson’s disease. Ann Indian Acad Neurol 2020; 23(1): 44-7.
[PMID: 32055121]
Kostic V, Przedborski S, Flaster E, Sternic N. Early development of levodopa-induced dyskinesias and response fluctuations in young-onset Parkinson’s disease. Neurology 1991; 41(2 (Pt 1)): 202-5.
[] [PMID: 1992362]
Smith Y, Wichmann T, Factor SA, DeLong MR. Parkinson’s disease therapeutics: new developments and challenges since the introduction of levodopa. Neuropsychopharmacology 2012; 37(1): 213-46.
[] [PMID: 21956442]
Gallagher DA, Lees AJ, Schrag A. What are the most important nonmotor symptoms in patients with Parkinson’s disease and are we missing them? Mov Disord 2010; 25(15): 2493-500.
[] [PMID: 20922807]
Fahn S, Cohen G. The oxidant stress hypothesis in Parkinson’s disease: evidence supporting it. Ann Neurol 1992; 32(6): 804-12.
[] [PMID: 1471873]
Fahn S, Oakes D, Shoulson I, et al. Levodopa and the progression of Parkinson’s disease. N Engl J Med 2004; 351(24): 2498-508.
[] [PMID: 15590952]
Riederer P, Müller T. Monoamine oxidase-B inhibitors in the treatment of Parkinson’s disease: clinical-pharmacological aspects. J Neural Transm (Vienna) 2018; 125(11): 1751-7.
[] [PMID: 29569037]
Korczyn AD, Brunt ER, Larsen JP, Nagy Z, Poewe WH, Ruggieri S. A 3-year randomized trial of ropinirole and bromocriptine in early Parkinson’s disease. The 053 Study Group. Neurology 1999; 53(2): 364-70.
[] [PMID: 10430427]
Rascol O, Brooks DJ, Brunt ER, Korczyn AD, Poewe WH, Stocchi F. Ropinirole in the treatment of early Parkinson’s disease: a 6-month interim report of a 5-year levodopa-controlled study. 056 Study Group. Mov Disord 1998; 13(1): 39-45.
[] [PMID: 9452324]
Reichmann H. Long-term treatment with dopamine agonists in idiopathic Parkinson's disease J Neurol 2000. 247 Suppl 4: IV/17-9.
Montastruc JL, Rascol O, Senard JM. Treatment of Parkinson’s disease should begin with a dopamine agonist. Mov Disord 1999; 14(5): 725-30.
[<725:AIDMDS1003>3.0.CO;2-L] [PMID: 10495032]
Micieli G, Martignoni E, Cavallini A, et al. Lisuride and bromocryptine in L-Dopa stable-responder parkinsonian patients: a comparative, double-blind evaluation of cardiopressor and neurochemical effects. Funct Neurol 1996; 11(6): 317-25.
[PMID: 9074912]
Thorlund K, Wu P, Druyts E, Eapen S, Mills EJ. Nonergot dopamine-receptor agonists for treating Parkinson’s disease - a network meta-analysis. Neuropsychiatr Dis Treat 2014; 10: 767-76.
[] [PMID: 24855362]
Gungabissoon U, Kirichek O, El Baou C, Galwey N. Comparison of long-term use of prolonged-release ropinirole and immediaterelease dopamine agonists in an observational study in patients with Parkinson’s disease. Pharmacoepidemiol Drug Saf 2020; 29(5): 591-8.
[] [PMID: 32153056]
Rewane A, Nagalli S. Ropinirole. Treasure Island, FL: StatPearls 2020.
Gottwald MD, Bainbridge JL, Dowling GA, Aminoff MJ, Alldredge BK. New pharmacotherapy for Parkinson’s disease. Ann Pharmacother 1997; 31(10): 1205-17.
[] [PMID: 9337447]
Bibbiani F, Oh JD, Petzer JP, et al. A2A antagonist prevents dopamine agonist-induced motor complications in animal models of Parkinson’s disease. Exp Neurol 2003; 184(1): 285-94.
[] [PMID: 14637099]
Antonini A, Poewe W. Adenosine A2A receptor antagonists in Parkinson’s disease: still in the running. Lancet Neurol 2014; 13(8): 748-9.
[] [PMID: 25008550]
Calon F, Dridi M, Hornykiewicz O, Bédard PJ, Rajput AH, Di Paolo T. Increased adenosine A2A receptors in the brain of Parkinson’s disease patients with dyskinesias. Brain 2004; 127(Pt 5): 1075-84.
[] [PMID: 15033896]
Hauser RA, Olanow CW, Kieburtz KD, et al. Tozadenant (SYN115) in patients with Parkinson’s disease who have motor fluctuations on levodopa: a phase 2b, double-blind, randomised trial. Lancet Neurol 2014; 13(8): 767-76.
[] [PMID: 25008546]
LeWitt PA, Guttman M, Tetrud JW, et al. Adenosine A2A receptor antagonist istradefylline (KW-6002) reduces “off” time in Parkinson’s disease: a double-blind, randomized, multicenter clinical trial (6002-US-005). Ann Neurol 2008; 63(3): 295-302.
[] [PMID: 18306243]
Pourcher E, Fernandez HH, Stacy M, Mori A, Ballerini R, Chaikin P. Istradefylline for Parkinson’s disease patients experiencing motor fluctuations: results of the KW-6002-US-018 study. Parkinsonism Relat Disord 2012; 18(2): 178-84.
[] [PMID: 22000279]
Dungo R, Deeks ED. Istradefylline: first global approval. Drugs 2013; 73(8): 875-82.
[] [PMID: 23700273]
Takahashi M, Fujita M, Asai N, Saki M, Mori A. Safety and effectiveness of istradefylline in patients with Parkinson’s disease: interim analysis of a post-marketing surveillance study in Japan. Expert Opin Pharmacother 2018; 19(15): 1635-42.
[] [PMID: 30281377]
Torti M, Vacca L, Stocchi F. Istradefylline for the treatment of Parkinson’s disease: is it a promising strategy? Expert Opin Pharmacother 2018; 19(16): 1821-8.
[] [PMID: 30232916]
Hussar DA. New Drugs 2020, part 1. Nursing 2020; 50: 31-8.
Paton DM. Istradefylline: adenosine A2A receptor antagonist to reduce “OFF” time in Parkinson’s disease. Drugs Today (Barc) 2020; 56(2): 125-34.
[] [PMID: 32163528]
Blandini F, Porter RH, Greenamyre JT. Glutamate and Parkinson’s disease. Mol Neurobiol 1996; 12(1): 73-94.
[] [PMID: 8732541]
Lynch DR, Guttmann RP. Excitotoxicity: perspectives based on Nmethyl-D-aspartate receptor subtypes. J Pharmacol Exp Ther 2002; 300(3): 717-23.
[] [PMID: 11861773]
Koutsilieri E, Riederer P. Excitotoxicity and new antiglutamatergic strategies in Parkinson’s disease and Alzheimer’s disease. Parkinsonism Relat Disord 2007; 13(Suppl. 3): S329-31.
[] [PMID: 18267259]
Vissel B, Krupp JJ, Heinemann SF, Westbrook GL. A use dependent tyrosine dephosphorylation of NMDA receptors is independent of ion flux. Nat Neurosci 2001; 4(6): 587-96.
[] [PMID: 11369939]
Metman LV, Del Dotto P, LePoole K, Konitsiotis S, Fang J, Chase TN. Amantadine for levodopa-induced dyskinesias: a 1-year follow-up study. Arch Neurol 1999; 56(11): 1383-6.
[] [PMID: 10555659]
Moreau C, Delval A, Tiffreau V, et al. Memantine for axial signs in Parkinson’s disease: a randomised, double-blind, placebo controlled pilot study. J Neurol Neurosurg Psychiatry 2013; 84(5): 552-5.
[] [PMID: 23077087]
Paoletti P, Neyton J. NMDA receptor subunits: function and pharmacology. Curr Opin Pharmacol 2007; 7(1): 39-47.
[] [PMID: 17088105]
Nash JE, Brotchie JM. Characterisation of striatal NMDA receptors involved in the generation of parkinsonian symptoms: intrastriatal microinjection studies in the 6-OHDA-lesioned rat. Mov Disord 2002; 17(3): 455-66.
[] [PMID: 12112191]
Gogas KR. Glutamate-based therapeutic approaches: NR2B receptor antagonists. Curr Opin Pharmacol 2006; 6(1): 68-74.
[] [PMID: 16376149]
Wessell RH, Ahmed SM, Menniti FS, Dunbar GL, Chase TN, Oh JD. NR2B selective NMDA receptor antagonist CP-101,606 prevents levodopa-induced motor response alterations in hemi parkinsonian rats. Neuropharmacology 2004; 47(2): 184-94.
[] [PMID: 15223297]
Nash JE, Fox SH, Henry B, et al. Antiparkinsonian actions of ifenprodil in the MPTP-lesioned marmoset model of Parkinson’s disease. Exp Neurol 2000; 165(1): 136-42.
[] [PMID: 10964492]
Duty S. Targeting glutamate receptors to tackle the pathogenesis, clinical symptoms and levodopa-induced dyskinesia associated with Parkinson’s disease. CNS Drugs 2012; 26(12): 1017-32.
[] [PMID: 23114872]
Eggert K, Squillacote D, Barone P, et al. Safety and efficacy of perampanel in advanced Parkinson’s disease: a randomized, placebo-controlled study. Mov Disord 2010; 25(7): 896-905.
[] [PMID: 20461807]
Kobylecki C, Burn DJ, Kass-Iliyya L, Kellett MW, Crossman AR, Silverdale MA. Randomized clinical trial of topiramate for levodopa-induced dyskinesia in Parkinson’s disease. Parkinsonism Relat Disord 2014; 20(4): 452-5.
[] [PMID: 24521874]
Conn PJ, Battaglia G, Marino MJ, Nicoletti F. Metabotropic glutamate receptors in the basal ganglia motor circuit. Nat Rev Neurosci 2005; 6(10): 787-98.
[] [PMID: 16276355]
Bezard E, Pioli EY, Li Q, et al. The mGluR5 negative allosteric modulator dipraglurant reduces dyskinesia in the MPTP macaque model. Mov Disord 2014; 29(8): 1074-9.
[] [PMID: 24865335]
Stocchi F, Rascol O, Destee A, et al. AFQ056 in Parkinson patients with levodopa-induced dyskinesia: 13-week, randomized, dose finding study. Mov Disord 2013; 28(13): 1838-46.
[] [PMID: 23853029]
Tison F, Keywood C, Wakefield M, et al. A phase 2A trial of the novel mGluR5-negative allosteric modulator dipraglurant for levodopa-induced dyskinesia in Parkinson’s disease. Mov Disord 2016; 31(9): 1373-80.
[] [PMID: 27214664]
Petrov D, Pedros I, de Lemos ML, et al. Mavoglurant as a treatment for Parkinson’s disease. Expert Opin Investig Drugs 2014; 23(8): 1165-79.
[] [PMID: 24960254]
Kumar R, Hauser RA, Mostillo J, et al. Mavoglurant (AFQ056) in combination with increased levodopa dosages in Parkinson’s disease patients. Int J Neurosci 2016; 126(1): 20-4.
[] [PMID: 24007304]
Liu C. Targeting the cholinergic system in Parkinson’s disease. Acta Pharmacol Sin 2020; 41(4): 453-63.
[] [PMID: 32132659]
Ztaou S, Amalric M. Contribution of cholinergic interneurons to striatal pathophysiology in Parkinson’s disease. Neurochem Int 2019; 126: 1-10.
[] [PMID: 30825602]
Moehle MS, Conn PJ. Roles of the M4 acetylcholine receptor in the basal ganglia and the treatment of movement disorders. Mov Disord 2019; 34(8): 1089-99.
[] [PMID: 31211471]
Sadeh M, Braham J, Modan M. Effects of anticholinergic drugs on memory in Parkinson’s disease. Arch Neurol 1982; 39(10): 666-7.
[] [PMID: 7125982]
Brocks DR. Anticholinergic drugs used in Parkinson’s disease: an overlooked class of drugs from a pharmacokinetic perspective. J Pharm Pharm Sci 1999; 2(2): 39-46.
[PMID: 10952768]
Chambers NE, Meadows SM, Taylor A, et al. Effects of muscarinic acetylcholine m1 and m4 receptor blockade on dyskinesia in the Hemi-Parkinsonian Rat. Neuroscience 2019; 409: 180-94.
[] [PMID: 31029732]
Kish SJ. Biochemistry of Parkinson’s disease: is a brain serotonergic deficiency a characteristic of idiopathic Parkinson’s disease? Adv Neurol 2003; 91: 39-49.
[PMID: 12442662]
Carta M, Carlsson T, Kirik D, Björklund A. Dopamine released from 5-HT terminals is the cause of L-DOPA-induced dyskinesia in parkinsonian rats. Brain 2007; 130(Pt 7): 1819-33.
[] [PMID: 17452372]
Politis M, Wu K, Loane C, et al. Serotonergic mechanisms responsible for levodopa-induced dyskinesias in Parkinson’s disease patients. J Clin Invest 2014; 124(3): 1340-9.
[] [PMID: 24531549]
Olanow CW, Damier P, Goetz CG, et al. Multicenter, open-label, trial of sarizotan in Parkinson disease patients with levodopa induced dyskinesias (the SPLENDID Study). Clin Neuropharmacol 2004; 27(2): 58-62.
[] [PMID: 15252265]
Bezard E, Tronci E, Pioli EY, et al. Study of the antidyskinetic effect of eltoprazine in animal models of levodopa-induced dyskinesia. Mov Disord 2013; 28(8): 1088-96.
[] [PMID: 23389842]
Marsh L. Depression and Parkinson’s disease: current knowledge. Curr Neurol Neurosci Rep 2013; 13(12): 409.
[] [PMID: 24190780]
Menza M, Dobkin RD, Marin H, et al. The impact of treatment of depression on quality of life, disability and relapse in patients with Parkinson’s disease. Mov Disord 2009; 24(9): 1325-32.
[] [PMID: 19412944]
Ballanger B, Klinger H, Eche J, et al. Role of serotonergic 1A receptor dysfunction in depression associated with Parkinson’s disease. Mov Disord 2012; 27(1): 84-9.
[] [PMID: 21994070]
Richard IH, McDermott MP, Kurlan R, et al. A randomized, double-blind, placebo-controlled trial of antidepressants in Parkinson disease. Neurology 2012; 78(16): 1229-36.
[] [PMID: 22496199]
McMillan PJ, White SS, Franklin A, et al. Differential response of the central noradrenergic nervous system to the loss of locus coeruleus neurons in Parkinson’s disease and Alzheimer’s disease. Brain Res 2011; 1373: 240-52.
[] [PMID: 21147074]
Gesi M, Soldani P, Giorgi FS, Santinami A, Bonaccorsi I, Fornai F. The role of the locus coeruleus in the development of Parkinson’s disease. Neurosci Biobehav Rev 2000; 24(6): 655-68.
[] [PMID: 10940440]
Rommelfanger KS, Edwards GL, Freeman KG, Liles LC, Miller GW, Weinshenker D. Norepinephrine loss produces more profound motor deficits than MPTP treatment in mice. Proc Natl Acad Sci USA 2007; 104(34): 13804-9.
[] [PMID: 17702867]
Rascol O, Arnulf I, Peyro-Saint Paul H, et al. Idazoxan, an alpha-2 antagonist, and L-DOPA-induced dyskinesias in patients with Parkinson’s disease. Mov Disord 2001; 16(4): 708-13.
[] [PMID: 11481696]
Johnston TH, Fox SH, Piggott MJ, Savola JM, Brotchie JM. The α2 adrenergic antagonist fipamezole improves quality of levodopa action in Parkinsonian primates. Mov Disord 2010; 25(13): 2084-93.
[] [PMID: 20824735]
Lewitt PA, Hauser RA, Lu M, et al. Randomized clinical trial of fipamezole for dyskinesia in Parkinson disease (FJORD study). Neurology 2012; 79(2): 163-9.
[] [PMID: 22744665]
Bonci A, Grillner P, Mercuri NB, Bernardi G. L-Type calcium channels mediate a slow excitatory synaptic transmission in rat midbrain dopaminergic neurons. J Neurosci 1998; 18(17): 6693-703.
[] [PMID: 9712641]
Striessnig J, Koschak A, Sinnegger-Brauns MJ, et al. Role of voltage-gated L-type Ca2+ channel isoforms for brain function. Biochem Soc Trans 2006; 34(Pt 5): 903-9.
[] [PMID: 17052224]
Stark AK, Pakkenberg B. Histological changes of the dopaminergic nigrostriatal system in aging. Cell Tissue Res 2004; 318(1): 81-92.
[] [PMID: 15365813]
Chan CS, Gertler TS, Surmeier DJ. A molecular basis for the increased vulnerability of substantia nigra dopamine neurons in aging and Parkinson’s disease. Mov Disord 2010; 25(Suppl. 1): S63-70.
[] [PMID: 20187241]
Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 2005; 39: 359-407.
[] [PMID: 16285865]
Ilijic E, Guzman JN, Surmeier DJ. The L-type channel antagonist isradipine is neuroprotective in a mouse model of Parkinson’s disease. Neurobiol Dis 2011; 43(2): 364-71.
[] [PMID: 21515375]
Simuni T, Borushko E, Avram MJ, et al. Tolerability of isradipine in early Parkinson’s disease: a pilot dose escalation study. Mov Disord 2010; 25(16): 2863-6.
[] [PMID: 20818667]
Youdim MB, Edmondson D, Tipton KF. The therapeutic potential of monoamine oxidase inhibitors. Nat Rev Neurosci 2006; 7(4): 295-309.
[] [PMID: 16552415]
Bar Am O, Amit T, Youdim MB. Contrasting neuroprotective and neurotoxic actions of respective metabolites of anti-Parkinson drugs rasagiline and selegiline. Neurosci Lett 2004; 355(3): 169-72.
[] [PMID: 14732458]
McCormack PL. Rasagiline: a review of its use in the treatment of idiopathic Parkinson’s disease. CNS Drugs 2014; 28(11): 1083-97.
[] [PMID: 25322951]
Nayak L, Henchcliffe C. Rasagiline in treatment of Parkinson’s disease. Neuropsychiatr Dis Treat 2008; 4(1): 23-32.
[PMID: 18728823]
Malaty IA, Fernandez HH. Role of rasagiline in treating Parkinson’s disease: effect on disease progression. Ther Clin Risk Manag 2009; 5(4): 413-9.
[PMID: 19753135]
Tábi T, Szökő E, Vécsei L, Magyar K. The pharmacokinetic evaluation of selegiline ODT for the treatment of Parkinson’s disease. Expert Opin Drug Metab Toxicol 2013; 9(5): 629-36.
[] [PMID: 23506388]
Olanow CW, Fahn S, Langston JW, Godbold J. Selegiline and mortality in Parkinson’s disease. Ann Neurol 1996; 40(6): 841-5.
[] [PMID: 9007088]
Lees AJ, Head J, Shlomo YB. Selegiline and mortality in Parkinson’s disease: another view. Ann Neurol 1997; 41(2): 282-3.
[] [PMID: 9029081]
Sari Y, Khalil A. Monoamine oxidase inhibitors extracted from tobacco smoke as neuroprotective factors for potential treatment of Parkinson’s disease. CNS Neurol Disord Drug Targets 2015; 14: 777-85.
Jung UJ, Leem E, Kim SR. Naringin: a protector of the nigrostriatal dopaminergic projection. Exp Neurobiol 2014; 23(2): 124-9.
[] [PMID: 24963276]
Chauhan NB, Siegel GJ, Lee JM. Depletion of glial cell line derived neurotrophic factor in substantia nigra neurons of Parkinson’s disease brain. J Chem Neuroanat 2001; 21(4): 277-88.
[] [PMID: 11429269]
Torres N, Molet J, Moro C, Mitrofanis J, Benabid AL. Neuroprotective surgical strategies in Parkinson’s disease: role of preclinical data. Int J Mol Sci 2017; 18(10): 2190.
Choi-Lundberg DL, Lin Q, Chang Y-N, et al. Dopaminergic neurons protected from degeneration by GDNF gene therapy. Science 1997; 275(5301): 838-41.
[] [PMID: 9012352]
Lapchak PA, Miller PJ, Collins F, Jiao S. Glial cell line-derived neurotrophic factor attenuates behavioural deficits and regulates nigrostriatal dopaminergic and peptidergic markers in 6-hydroxydopamine-lesioned adult rats: comparison of intraventricular and intranigral delivery. Neuroscience 1997; 78(1): 61-72.
[] [PMID: 9135089]
Lapchak PA, Jiao S, Collins F, Miller PJ. Glial cell line-derived neurotrophic factor: distribution and pharmacology in the rat following a bolus intraventricular injection. Brain Res 1997; 747(1): 92-102.
[] [PMID: 9042532]
Date I, Aoi M, Tomita S, Collins F, Ohmoto TJN. GDNF administration induces recovery of the nigrostriatal dopaminergic system both in young and aged parkinsonian mice. Neuroreport 1998; 9(10): 2365-9.
Tomac A, Lindqvist E, Lin L-F, et al. Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo. Nature 1995; 373(6512): 335-9.
Grondin R, Zhang Z, Yi A, et al. Chronic, controlled GDNF infusion promotes structural and functional recovery in advanced parkinsonian monkeys. Brain 2002; 125(Pt 10): 2191-201.
Decressac M, Ulusoy A, Mattsson B, et al. GDNF fails to exert neuroprotection in a rat α-synuclein model of Parkinson’s disease. Brain 2011; 134(Pt 8): 2302-11.
Decressac M, Kadkhodaei B, Mattsson B, Laguna A, Perlmann T, Björklund A. α-Synuclein–induced down-regulation of Nurr1 disrupts GDNF signaling in nigral dopamine neurons. Sci Transl Med 2012; 4(163): 163ra156.
Horger BA, Nishimura MC, Armanini MP, et al. Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons. J Neurosci 1998; 18(13): 4929-37.
Oiwa Y, Yoshimura R, Nakai K, Itakura T. Dopaminergic neuroprotection and regeneration by neurturin assessed by using behavioral, biochemical and histochemical measurements in a model of progressive Parkinson’s disease. Brain Res 2002; 947(2): 271-83.
[] [PMID: 12176170]
Li H, He Z, Su T, et al. Protective action of recombinant neurturin on dopaminergic neurons in substantia nigra in a rhesus monkey model of Parkinson’s disease. Neurol Res 2003; 25(3): 263-7.
Reyes-Corona D, Vazquez-Hernandez N, Escobedo L, et al. Neurturin overexpression in dopaminergic neurons induces presynaptic and postsynaptic structural changes in rats with chronic 6-hydroxydopamine lesion. PLoS One 2017; 12(11): e0188239.
Herzog CD, Brown L, Kruegel BR, et al. Enhanced neurotrophic distribution, cell signaling and neuroprotection following substantia nigral versus striatal delivery of AAV2-NRTN (CERE-120). Neurobiol Dis 2013; 58: 38-48.
Gasmi M, Brandon EP, Herzog CD, et al. AAV2-mediated delivery of human neurturin to the rat nigrostriatal system: long-term efficacy and tolerability of CERE-120 for Parkinson’s disease. Neurobiol Dis 2007; 27: 67-76.
Fjord-Larsen L, Johansen JL, Kusk P, et al. Efficient in vivo protection of nigral dopaminergic neurons by lentiviral gene transfer of a modified Neurturin construct. Exp Neurol 2005; 195(1): 49-60.
Herzog CD, Dass B, Gasmi M, et al. Transgene expression, bioactivity, and safety of CERE-120 (AAV2-neurturin) following delivery to the monkey striatum. Mol Ther 2008; 16(10): 1737-44.
Levivier M, Przedborski S, Bencsics C, Kang UJ. Intrastriatal implantation of fibroblasts genetically engineered to produce brain derived neurotrophic factor prevents degeneration of dopaminergic neurons in a rat model of Parkinson’s disease. J Neurosci 1995; 15(12): 7810-20.
[] [PMID: 8613721]
Yoshimoto Y, Lin Q, Collier TJ, Frim DM, Breakefield XO, Bohn MC. Astrocytes retrovirally transduced with BDNF elicit behavioral improvement in a rat model of Parkinson’s disease. Brain Res 1995; 691(1-2): 25-36.
[] [PMID: 8590062]
Klein RL, Lewis MH, Muzyczka N, Meyer EM. Prevention of 6-hydroxydopamine-induced rotational behavior by BDNF somatic gene transfer. Brain Res 1999; 847(2): 314-20.
[] [PMID: 10575102]
Sun M, Kong L, Wang X, Lu XG, Gao Q, Geller AI. Comparison of the capability of GDNF, BDNF, or both, to protect nigrostriatal neurons in a rat model of Parkinson’s disease. Brain Res 2005; 1052(2): 119-29.
[] [PMID: 16018990]
Funa K, Yamada N, Brodin G, et al. Enhanced synthesis of platelet-derived growth factor following injury induced by 6-hydroxydopamine in rat brain. Neuroscience 1996; 74(3): 825-33.
Padel T, Özen I, Boix J, et al. Platelet-derived growth factor-BB has neurorestorative effects and modulates the pericyte response in a partial 6-hydroxydopamine lesion mouse model of Parkinson's disease. Neurobiol Dis 2016; 94: 95-105.
Zachrisson O, Zhao M, Andersson A, et al. Restorative effects of platelet derived growth factor-BB in rodent models of Parkinson's disease. J Parkinsons Dis 2011; 1(1): 49-63.
Voutilainen MH, Bäck S, Peränen J, et al. Chronic infusion of CDNF prevents 6-OHDA-induced deficits in a rat model of Parkinson's disease 2011; 228: 98-108.
Airavaara M, Harvey BK, Voutilainen MH, et al. CDNF protects the nigrostriatal dopamine system and promotes recovery after MPTP treatment in mice. Cell Transplant 2012; 21(6): 1213-23.
Ren X, Zhang T, Gong X, Hu G, Ding W. Wang XJEn. AAV2-mediated striatum delivery of human CDNF prevents the deterioration of midbrain dopamine neurons in a 6-hydroxydopamine induced parkinsonian rat model. Exp Neurol 2013; 248: 148-56.
Cordero-Llana Ó, Houghton BC, Rinaldi F, et al. Enhanced efficacy of the CDNF/MANF family by combined intranigral overexpression in the 6-OHDA rat model of Parkinson’s disease. Mol Ther 2015; 23: 244-54.
Voutilainen MH, De Lorenzo F, Stepanova P, et al. Evidence for an additive neurorestorative effect of simultaneously administered CDNF and GDNF in hemiparkinsonian rats: implications for different mechanism of action. eNeuro 2017; 4(1) : ENEURO.0117-16.2017.
Rodrigues TM, Jerónimo-Santos A, Outeiro TF, Sebastião AM, Diógenes MJ. Challenges and promises in the development of neurotrophic factor-based therapies for Parkinson’s disease. Drugs Aging 2014; 31(4): 239-61.
[] [PMID: 24610720]
Knüsel B, Winslow JW, Rosenthal A, et al. Promotion of central cholinergic and dopaminergic neuron differentiation by brain derived neurotrophic factor but not neurotrophin 3. Proc Natl Acad Sci USA 1991; 88(3): 961-5.
[] [PMID: 1992488]
Lorigados Pedre L, Pavón Fuentes N, Alvarez González L, et al. Nerve growth factor levels in Parkinson disease and experimental parkinsonian rats. Brain Res 2002; 952(1): 122-7.
[] [PMID: 12363411]
Mogi M, Togari A, Kondo T, et al. Brain-derived growth factor and nerve growth factor concentrations are decreased in the substantia nigra in Parkinson’s disease. Neurosci Lett 1999; 270(1): 45-8.
[] [PMID: 10454142]
Eliash S, Dror V, Cohen S, Rehavi M. Neuroprotection by rasagiline in thiamine deficient rats. Brain Res 2009; 1256: 138-48.
[] [PMID: 19103184]
Inaba-Hasegawa K, Akao Y, Maruyama W, Naoi M. Type A monoamine oxidase is associated with induction of neuroprotective Bcl-2 by rasagiline, an inhibitor of type B monoamine oxidase. J Neural Transm (Vienna) 2012; 119(4): 405-14.
[] [PMID: 22065207]
Naoi M, Maruyama W. Monoamine oxidase inhibitors as neuroprotective agents in age-dependent neurodegenerative disorders. Curr Pharm Des 2010; 16(25): 2799-817.
[] [PMID: 20698822]
Naoi M, Maruyama W, Inaba-Hasegawa K. Revelation in the neuroprotective functions of rasagiline and selegiline: the induction of distinct genes by different mechanisms. Expert Rev Neurother 2013; 13(6): 671-84.
[] [PMID: 23739004]
Weinreb O, Amit T, Bar-Am O, Youdim MB. Rasagiline: a novel anti-Parkinsonian monoamine oxidase-B inhibitor with neuroprotective activity. Prog Neurobiol 2010; 92(3): 330-44.
[] [PMID: 20600573]
Semkova I, Wolz P, Schilling M, Krieglstein J. Selegiline enhances NGF synthesis and protects central nervous system neurons from excitotoxic and ischemic damage. Eur J Pharmacol 1996; 315(1): 19-30.
[] [PMID: 8960860]

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