免疫抑制改变少年型神经鞘脂沉积病小鼠的疾病严重程度。
Immunosuppression alters disease severity in juvenile Batten disease mice.
机构信息
Center for Neural Development & Disease, University of Rochester School of Medicine & Dentistry, Rochester, NY, United States.
出版信息
J Neuroimmunol. 2011 Jan;230(1-2):169-72. doi: 10.1016/j.jneuroim.2010.08.024.
Abstract
Autoantibodies to brain proteins are present in Juvenile Neuronal Ceroid Lipofuscinosis (Batten disease) patients and in the Cln3-/- mouse model of this disease, suggesting an autoimmune component to pathogenesis. Using genetic or pharmaceutical approaches to attenuate this immune response in Cln3-/- mice, we demonstrate decreased neuroinflammation, decreased deposition of immunoglobulin G in the brain and protection of vulnerable neuron populations. Moreover, immune suppression results in a significant improvement in motor performance providing for the first plausible therapeutic approach for juvenile Batten disease.
摘要
脑蛋白自身抗体存在于少年神经元蜡样脂褐质沉积症（Batten 病）患者和该疾病的 Cln3-/- 小鼠模型中，提示发病机制中有自身免疫成分。我们使用遗传或药物方法来减弱 Cln3-/- 小鼠的这种免疫反应，结果显示神经炎症减少，脑内免疫球蛋白 G 沉积减少，以及易损神经元群体得到保护。此外，免疫抑制可显著改善运动功能，为少年 Batten 病提供了首个合理的治疗方法。
相似文献
1
Immunosuppression alters disease severity in juvenile Batten disease mice.
J Neuroimmunol. 2011 Jan;230(1-2):169-72. doi: 10.1016/j.jneuroim.2010.08.024.
2
Age-dependent therapeutic effect of memantine in a mouse model of juvenile Batten disease.
Neuropharmacology. 2012 Oct;63(5):769-75. doi: 10.1016/j.neuropharm.2012.05.040. Epub 2012 Jun 6.
3
Self-Complementary AAV9 Gene Delivery Partially Corrects Pathology Associated with Juvenile Neuronal Ceroid Lipofuscinosis (CLN3).
J Neurosci. 2016 Sep 14;36(37):9669-82. doi: 10.1523/JNEUROSCI.1635-16.2016.
4
Immunosuppressive Treatment for Retinal Degeneration in Juvenile Neuronal Ceroid Lipofuscinosis (Juvenile Batten Disease).
Ophthalmic Genet. 2015;36(4):359-64. doi: 10.3109/13816810.2014.886271. Epub 2014 Feb 19.
5
Efficacy of phosphodiesterase-4 inhibitors in juvenile Batten disease (CLN3).
Ann Neurol. 2016 Dec;80(6):909-923. doi: 10.1002/ana.24815. Epub 2016 Nov 23.
6
Attenuation of AMPA receptor activity improves motor skills in a mouse model of juvenile Batten disease.
Exp Neurol. 2008 Jan;209(1):288-91. doi: 10.1016/j.expneurol.2007.09.012. Epub 2007 Oct 25.
7
Fingolimod and Teriflunomide Attenuate Neurodegeneration in Mouse Models of Neuronal Ceroid Lipofuscinosis.
Mol Ther. 2017 Aug 2;25(8):1889-1899. doi: 10.1016/j.ymthe.2017.04.021. Epub 2017 May 13.
8
Glial cells are functionally impaired in juvenile neuronal ceroid lipofuscinosis and detrimental to neurons.
Acta Neuropathol Commun. 2017 Oct 17;5(1):74. doi: 10.1186/s40478-017-0476-y.
9
Regional brain atrophy in mouse models of neuronal ceroid lipofuscinosis: a new rostrocaudal perspective.
J Child Neurol. 2013 Sep;28(9):1117-22. doi: 10.1177/0883073813494479.
10
An autoantibody inhibitory to glutamic acid decarboxylase in the neurodegenerative disorder Batten disease.
Hum Mol Genet. 2002 Jun 1;11(12):1421-31. doi: 10.1093/hmg/11.12.1421.
引用本文的文献
1
Neuronal ceroid lipofuscinosis: underlying mechanisms and emerging therapeutic targets.
Nat Rev Neurol. 2025 Sep 4. doi: 10.1038/s41582-025-01132-4.
2
Gene therapy ameliorates neuromuscular pathology in CLN3 disease.
Acta Neuropathol Commun. 2025 Jul 23;13(1):160. doi: 10.1186/s40478-025-02059-z.
3
Unraveling the link between neuropathy target esterase NTE/SWS, lysosomal storage diseases, inflammation, abnormal fatty acid metabolism, and leaky brain barrier.
Elife. 2024 Apr 25;13:e98020. doi: 10.7554/eLife.98020.
4
Early recognition of CLN3 disease facilitated by visual electrophysiology and multimodal imaging.
Doc Ophthalmol. 2023 Jun;146(3):241-256. doi: 10.1007/s10633-023-09930-1. Epub 2023 Mar 25.
5
The Role of Alpha-Synuclein Autoantibodies in the Induction of Brain Inflammation and Neurodegeneration in Aged Humans.
Front Aging Neurosci. 2022 May 26;14:902191. doi: 10.3389/fnagi.2022.902191. eCollection 2022.
6
Recent Insight into the Genetic Basis, Clinical Features, and Diagnostic Methods for Neuronal Ceroid Lipofuscinosis.
Int J Mol Sci. 2022 May 20;23(10):5729. doi: 10.3390/ijms23105729.
7
Experimental Therapeutic Approaches for the Treatment of Retinal Pathology in Neuronal Ceroid Lipofuscinoses.
Front Neurol. 2022 Apr 18;13:866983. doi: 10.3389/fneur.2022.866983. eCollection 2022.
8
Glial Dysfunction and Its Contribution to the Pathogenesis of the Neuronal Ceroid Lipofuscinoses.
Front Neurol. 2022 Apr 4;13:886567. doi: 10.3389/fneur.2022.886567. eCollection 2022.
9
Patient-Derived Induced Pluripotent Stem Cell Models for Phenotypic Screening in the Neuronal Ceroid Lipofuscinoses.
Molecules. 2021 Oct 15;26(20):6235. doi: 10.3390/molecules26206235.
10
Advances in the Treatment of Neuronal Ceroid Lipofuscinosis.
Expert Opin Orphan Drugs. 2019;7(11):473-500. doi: 10.1080/21678707.2019.1684258. Epub 2019 Nov 27.
本文引用的文献
1
Cerebellar defects in a mouse model of juvenile neuronal ceroid lipofuscinosis.
Brain Res. 2009 Apr 17;1266:93-107. doi: 10.1016/j.brainres.2009.02.009. Epub 2009 Feb 20.
2
Attenuation of AMPA receptor activity improves motor skills in a mouse model of juvenile Batten disease.
Exp Neurol. 2008 Jan;209(1):288-91. doi: 10.1016/j.expneurol.2007.09.012. Epub 2007 Oct 25.
3
Identification of alpha-fetoprotein as an autoantigen in juvenile Batten disease.
Neurobiol Dis. 2008 Jan;29(1):92-102. doi: 10.1016/j.nbd.2007.08.007. Epub 2007 Aug 25.
4
IgG entry and deposition are components of the neuroimmune response in Batten disease.
Neurobiol Dis. 2007 Feb;25(2):239-51. doi: 10.1016/j.nbd.2006.09.005. Epub 2006 Oct 27.
5
Distinct patterns of serum immunoreactivity as evidence for multiple brain-directed autoantibodies in juvenile neuronal ceroid lipofuscinosis.
Neuropathol Appl Neurobiol. 2006 Oct;32(5):469-82. doi: 10.1111/j.1365-2990.2006.00738.x.
6
Molecular genetics of the NCLs -- status and perspectives.
Biochim Biophys Acta. 2006 Oct;1762(10):857-64. doi: 10.1016/j.bbadis.2006.05.006. Epub 2006 May 27.
7
Visual deficits in a mouse model of Batten disease are the result of optic nerve degeneration and loss of dorsal lateral geniculate thalamic neurons.
Neurobiol Dis. 2006 May;22(2):284-93. doi: 10.1016/j.nbd.2005.11.008. Epub 2006 Jan 18.
8
Autoimmunity to glutamic acid decarboxylase in the neurodegenerative disorder Batten disease.
Neurology. 2005 Feb 22;64(4):743-5. doi: 10.1212/01.WNL.0000151973.08426.7E.
9
Regional and cellular neuropathology in the palmitoyl protein thioesterase-1 null mutant mouse model of infantile neuronal ceroid lipofuscinosis.
Neurobiol Dis. 2004 Jul;16(2):346-59. doi: 10.1016/j.nbd.2004.02.010.
10
The genetic spectrum of human neuronal ceroid-lipofuscinoses.
Brain Pathol. 2004 Jan;14(1):70-6. doi: 10.1111/j.1750-3639.2004.tb00500.x.
Zotero 插件