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Cited by 132Parkinson's Disease Mechanisms and TreatmentsAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

Immunotherapy for neurodegenerative diseases: Focus on α-synucleinopathies

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Valera, Elvira, Masliah, Eliezer·2013·Pharmacology & Therapeutics
DOI 10.1016/j.pharmthera.2013.01.013PMC PMC3925783
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Abstract

Immunotherapy is currently being intensively explored as much-needed disease-modifying treatment for neurodegenerative diseases. While Alzheimer's disease (AD) has been the focus of numerous immunotherapeutic studies, less attention has been paid to Parkinson's disease (PD) and other neurodegenerative disorders. The reason for this difference is that the amyloid beta (Aβ) protein in AD is a secreted molecule that circulates in the blood and is readably recognized by antibodies. In contrast, α-synuclein (α-syn), tau, huntingtin and other proteins involved in neurodegenerative diseases have been considered to be exclusively of intracellular nature. However, the recent discovery that toxic oligomeric versions of α-syn and tau accumulate in the membrane and can be excreted to the extracellular environment has provided a rationale for the development of immunotherapeutic approaches for PD, dementia with Lewy bodies, frontotemporal dementia, and other neurodegenerative disorders characterized by the abnormal accumulation of these proteins. Active immunization, passive immunization, and T cell-mediated cellular immunotherapeutic approaches have been developed targeting Aβ, α-syn and tau. Most advanced studies, including results from phase III clinical trials for passive immunization in AD, have been recently reported. Results suggest that immunotherapy might be a promising therapeutic approach for neurodegenerative diseases that progress with the accumulation and propagation of toxic protein aggregates. In this manuscript we provide an overview on immunotherapeutic advances for neurodegenerative disorders, with special emphasis on α-synucleinopathies.

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  • Treating synucleinopathy animal models with drugs to reduce neuroinflammation decreases α-synuclein neuropathology.

    “but when these animals were treated with drugs to reduce neuroinflammation, α-synuclein neuropathology also decreased (57, 58).”

    From LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies (2020) · cites this paper as [58]

    Section 5 reports decreased α-synuclein accumulation in immunized mice. Section 8 reports that T-cell immunotherapy reduced neuroinflammatory responses and protected neurons, but does not report decreased α-synuclein pathology. Neither passage establishes the claimed sequence of drug treatment to reduce neuroinflammation followed by decreased α-synuclein neuropathology. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Valera, E., & Masliah, E.
Affiliations
University of California San Diego (US)
Corresponding author
Masliah, Eliezer
ORCID
Venue
Pharmacology & Therapeutics
Publisher
Elsevier BV
Published
2013-06
Volume
138
Issue
3
Pages
311-322
ISSN
0163-7258 (ISSN-L)
DOI
10.1016/j.pharmthera.2013.01.013
PMC
PMC3925783
OpenAlex
W2039334290
Cited by
132
References
22
Citations by year
2026: 7 · 2025: 3 · 2024: 9 · 2023: 7 · 2022: 9 · 2021: 9 · 2020: 7 · 2019: 9 · 2018: 14 · 2017: 12 · 2016: 12 · 2015: 14 · 2014: 13 · 2013: 7
FWCI
2.00
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Pharmacology & Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • NIH (AG18440, AG022074, NS044233)
  • Neotope Biosciences
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
immunotherapy, neurodegenerative diseases, synucleinopathies, alpha-synuclein, Parkinson's disease, dementia with Lewy bodies, frontotemporal dementia, Alzheimer's disease, amyloid-beta, tau protein, active immunization, passive immunization, T cell therapy, disease-modifying therapy
MeSH terms
Animals, Humans, Immunotherapy, Neurodegenerative Diseases, alpha-Synuclein

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