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Immunotherapy Strategies for Lewy Body and Parkinson's Diseases

  • Reference work entry
Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

Accumulation of α-synuclein (α-syn) resulting in the formation of oligomers and protofibrils has been linked to the neurodegenerative process in Parkinson’s disease and Lewy body dementia. Genetic and environmental factors affecting the rate of α-syn production, aggregation, and clearance might play an important role. Therefore, development of new therapies will require either reducing α-syn synthesis and rate of aggregation, or enhancing clearance. Clearance of α-syn aggregates depends on lysosomal and nonlysosomal pathways. Among the various approaches to promote clearance of α-syn aggregates, immunotherapy is of special interest because antibodies can specifically target abnormal α-syn aggregates. Experimental studies have shown that active as well as passive immunization might reduce α-syn accumulation and associated deficits. Similarly, strategies employing anti-α-syn intrabodies, where cells are genetically modified to produce anti-α-syn antibodies, rescue the phenotype associated with α-syn aggregates. In addition, cellular immunotherapy with copolymer has been shown to reduce neurodegeneration in acute models such as 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) toxicity. The mechanisms through which antibodies against α-syn aggregates might ameliorate the deficits in mice and cellular models are under investigation. Antibodies might act by recognizing α-syn oligomers accumulating in the neuronal membranes and promote degradation of α-syn aggregates via endosomal–lysosomal pathways and autophagy. Therapeutic approaches focusing on the combination of antibodies and regulation of cellular immune responses might prove in the future to be effective.

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Abbreviations

CMA:

chaperone-mediated autophagy

DLB:

dementia with LBs

LBD:

Lewy body disease

LRRK2:

leucine-rich repeat kinase-2

MPTP:

1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine

MSA:

multiple systems atrophy

PDD:

PD dementia

PDGF-β:

platelet-derived growth factor-β

PINK1:

PTEN-induced putative kinase-1

PrP:

prion protein

UCH-L1:

ubiquitin carboxyl-terminal esterase-L1

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Acknowledgments

This work was supported by NIH Grants AG18440, AG022074, and AG10435.

Authors
  1. L. Crews
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  2. B. Spencer
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  3. E. Masliah
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Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 10962, 140 Old Orangeburg Road, Orangeburg, New York, USA

    Abel Lajtha (Director) (Director)

  2. Department of Neurosciences Division of Neurology, Medical University of South Carolina, 29425, 96 Jonathan Lucas Street, Suite 309, Charleston, SC, USA

    Naren Banik

  3. Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, 29209, 6439 Garners Ferry Road Building 2, Room C11, Columbia, SC, USA

    Swapan K. Ray

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© 2009 Springer Science+Business Media, LLC

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Crews, L., Spencer, B., Masliah, E. (2009). Immunotherapy Strategies for Lewy Body and Parkinson's Diseases. In: Lajtha, A., Banik, N., Ray, S.K. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30375-8_26

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