Effects of alpha-synuclein immunization in a mouse model of Parkinson's disease

Author(s): Masliah E, Rockenstein E, Adame A, Alford M, Crews L, et al.

Abstract

Abnormal folding of alpha-synuclein (alpha-syn) is thought to lead to neurodegeneration and the characteristic symptoms of Lewy body disease (LBD). Since previous studies suggest that immunization might be a potential therapy for Alzheimer's disease, we hypothesized that immunization with human (h)alpha-syn might have therapeutic effects in LBD. For this purpose, halpha-syn transgenic (tg) mice were vaccinated with halpha-syn. In mice that produced high relative affinity antibodies, there was decreased accumulation of aggregated halpha-syn in neuronal cell bodies and synapses that was associated with reduced neurodegeneration. Furthermore, antibodies produced by immunized mice recognized abnormal halpha-syn associated with the neuronal membrane and promoted the degradation of halpha-syn aggregates, probably via lysosomal pathways. Similar effects were observed with an exogenously applied FITC-tagged halpha-syn antibody. These results suggest that vaccination is effective in reducing neuronal accumulation of halpha-syn aggregates and that further development of this approach might have a potential role in the treatment of LBD.

Similar Articles

Neuroprotective activities of CD4+CD25+ regulatory T cells in an animal model of Parkinson's disease

Author(s): Reynolds AD, Banerjee R, Liu J, Gendelman HE, Mosley RL

Alterations of T-lymphocyte populations in Parkinson disease

Author(s): Baba Y, Kuroiwa A, Uitti RJ, Wszolek ZK, Yamada T

Lymphocyte populations in Parkinson's disease and in rat models of parkinsonism

Author(s): Bas J, Calopa M, Mestre M, Molleví DG, Cutillas B, et al.

Apoptosis of peripheral blood lymphocytes in Parkinson patients

Author(s): Calopa M, Bas J, Callén A, Mestre M

The ABC of the blood-brain barrier - regulation of drug efflux pumps

Author(s): Mahringer A, Ott M, Reimold I, Reichel V, Fricker G

Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy

Author(s): van Vliet EA, da Costa Araújo S, Redeker S, van Schaik R, Aronica E, et al.

Blood-brain barrier disruption in multiple sclerosis

Author(s): Minagar A, Alexander JS

The role of neuroinflammation on the pathogenesis of Parkinson's disease

Author(s): Chung YC, Ko HW, Bok E, Park ES, Huh SH, et al.

Decreased blood-brain barrier P-glycoprotein function in the progression of Parkinson's disease, PSP and MSA

Author(s): Bartels AL, Willemsen AT, Kortekaas R, de Jong BM, de Vries R, et al.

Attenuation of AD-like neuropathology by harnessing peripheral immune cells: local elevation of IL-10 and MMP-9

Author(s): Koronyo-Hamaoui M, Ko MK, Koronyo Y, Azoulay D, Seksenyan A, et al.

Proteomic studies of nitrated alpha-synuclein microglia regulation by CD4+CD25+ T cells

Author(s): Reynolds AD, Stone DK, Mosley RL, Gendelman HE

Leptin and ghrelin concentrations and weight loss in Parkinson's disease

Author(s): Fiszer U, Michałowska M, Baranowska B, Wolińska-Witort E, Jeske W, et al.

Innate and adaptive immunity for the pathobiology of Parkinson's disease

Author(s): Stone DK, Reynolds AD, Mosley RL, Gendelman HE

Immunoprotection against toxic biomarkers is retained during Parkinson's disease progression

Author(s): Gruden MA, Sewell RD, Yanamandra K, Davidova TV, Kucheryanu VG, et al.

Anti-melanin antibodies are increased in sera in Parkinson's disease

Author(s): Double KL, Rowe DB, Carew-Jones FM, Hayes M, Chan DK, et al.

Human interleukin-10 gene transfer is protective in a rat model of Parkinson's disease

Author(s): Johnston LC, Su X, Maguire-Zeiss K, Horovitz K, Ankoudinova I, et al.

α-Synuclein and dopamine at the crossroads of Parkinson's disease

Author(s): Venda LL, Cragg SJ, Buchman VL, Wade-Martins R

Immunocytochemical analysis of tumor necrosis factor and its receptors in Parkinson's disease

Author(s): Boka G, Anglade P, Wallach D, Javoy-Agid F, Agid Y, et al.

T-cells in Alzheimer's disease

Author(s): Town T, Tan J, Flavell RA, Mullan M