Targets and Mechanisms in Prevention of Parkinson's Disease through Immunomodulatory Treatments

被引:29
作者
Chelpin, M. von Euler [1 ]
Vorup-Jensen, T. [1 ]
机构
[1] Aarhus Univ, Dept Biomed, Aarhus, Denmark
关键词
REGULATORY T-CELLS; MYELIN BASIC-PROTEIN; SYNUCLEIN ACTIVATES MICROGLIA; ALPHA-SYNUCLEIN; GLATIRAMER ACETATE; MOUSE MODEL; MULTIPLE-SCLEROSIS; DOPAMINERGIC-NEURONS; ALZHEIMERS-DISEASE; ADAPTIVE IMMUNITY;
D O I
10.1111/sji.12542
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Parkinson's disease (PD) is the second most common neurodegenerative disease in the world; however, there is no cure for it. Current treatments only relieve some of the symptoms, without ceasing the disease, and lose efficacy with prolonged treatment. Considerable evidence shows that persistent inflammatory responses, involving T cell infiltration and glial cell activation, are common characteristics of human patients and play a crucial role in the degeneration of dopaminergic neurons. Therefore, it is important to develop therapeutic strategies that can impede or halt the disease through the modulation of the peripheral immune system by aiming at controlling the existing neuroinflammation. Most of the immunomodulatory therapies designed for the treatment of Parkinsons disease are based on vaccines using AS or antibodies against it; yet, it is of significant interest to explore other formulations that could be used as therapeutic agents. Several vaccination procedures have shown that inducing regulatory T cells in the periphery is protective in PD animal models. In this regard, the formulation glatiramer acetate (Copaxone((R))), extensively used for the treatment of multiple sclerosis, could be a suitable candidate due to its capability to increase the number and suppressor capacity of regulatory T cells. In this review, we will present some of the recent immunomodulatory therapies for PD including vaccinations with AS or glatiramoids, or both, as treatments of PD pathology.
引用
收藏
页码:321 / 330
页数:10
相关论文
共 110 条
[1]   Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system [J].
Abeliovich, A ;
Schmitz, Y ;
Fariñas, I ;
Choi-Lundberg, D ;
Ho, WH ;
Castillo, PE ;
Shinsky, N ;
Verdugo, JMG ;
Armanini, M ;
Ryan, A ;
Hynes, M ;
Phillips, H ;
Sulzer, D ;
Rosenthal, A .
NEURON, 2000, 25 (01) :239-252
[2]  
AFFIRIS, 2016, BOOST VACCINATION DA
[3]   Copolymer 1 acts against the immunodominant epitope 82-100 of myelin basic protein by T cell receptor antagonism in addition to major histocompatibility complex blocking [J].
Aharoni, R ;
Teitelbaum, D ;
Arnon, R ;
Sela, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (02) :634-639
[4]   Copolymer 1 induces T cells of the T helper type 2 that crossreact with myelin basic protein and suppress experimental autoimmune encephalomyelitis [J].
Aharoni, R ;
Teitelbaum, D ;
Sela, M ;
Arnon, R .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (20) :10821-10826
[5]   Copolymer 1 inhibits manifestations of graft rejection [J].
Aharoni, R ;
Teitelbaum, D ;
Arnon, R ;
Sela, M .
TRANSPLANTATION, 2001, 72 (04) :598-605
[6]   GLATIRAMER ACETATE RESTORES THE DEFECTIVE ACTIVITY OF REGULATORY B CELLS IN SLE [J].
Amrouche, K. ;
Pers, J. O. ;
Hillion, S. ;
Jamin, C. .
ANNALS OF THE RHEUMATIC DISEASES, 2016, 75 :A29-A29
[7]   Alpha-Synuclein Cell-to-Cell Transfer and Seeding in Grafted Dopaminergic Neurons In Vivo [J].
Angot, Elodie ;
Steiner, Jennifer A. ;
Tome, Carla M. Lema ;
Ekstrom, Peter ;
Mattsson, Bengt ;
Bjorklund, Anders ;
Brundin, Patrik .
PLOS ONE, 2012, 7 (06)
[8]   Peripheral inflammation and neuroprotection: Systemic pretreatment with complete Freund's adjuvant reduces 6-hydroxydopamine toxicity in a rodent model of Parkinson's disease [J].
Armentero, Marie-Therese ;
Levandis, Giovanna ;
Nappi, Giuseppe ;
Bazzini, Eleonora ;
Blandini, Fabio .
NEUROBIOLOGY OF DISEASE, 2006, 24 (03) :492-505
[9]   Alterations of T-lymphocyte populations in Parkinson disease [J].
Baba, Y ;
Kuroiwa, A ;
Uitti, RJ ;
Wszolek, ZK ;
Yamada, T .
PARKINSONISM & RELATED DISORDERS, 2005, 11 (08) :493-498
[10]   Lipid Peroxidation Product 4-Hydroxy-2-Nonenal Promotes Seeding-Capable Oligomer Formation and Cell-to-Cell Transfer of α-Synuclein [J].
Bae, Eun-Jin ;
Ho, Dong-Hwan ;
Park, Eunbi ;
Jung, Jin Woo ;
Cho, Kyungcho ;
Hong, Ji Hye ;
Lee, He-Jin ;
Kim, Kwang Pyo ;
Lee, Seung-Jae .
ANTIOXIDANTS & REDOX SIGNALING, 2013, 18 (07) :770-783