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Immunotherapies for Aging-Related Neurodegenerative Diseases—Emerging Perspectives and New Targets

Neurological disorders such as Alzheimer’s disease (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD), and vascular dementia (VCID) have no disease-modifying treatments to date and now constitute a dementia crisis that affects 5 million in the USA and over 50 million worldwide. The most c...

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Autores principales: Kwon, Somin, Iba, Michiyo, Kim, Changyoun, Masliah, Eliezer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222955/
https://www.ncbi.nlm.nih.gov/pubmed/32347461
http://dx.doi.org/10.1007/s13311-020-00853-2
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author Kwon, Somin
Iba, Michiyo
Kim, Changyoun
Masliah, Eliezer
author_facet Kwon, Somin
Iba, Michiyo
Kim, Changyoun
Masliah, Eliezer
author_sort Kwon, Somin
collection PubMed
description Neurological disorders such as Alzheimer’s disease (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD), and vascular dementia (VCID) have no disease-modifying treatments to date and now constitute a dementia crisis that affects 5 million in the USA and over 50 million worldwide. The most common pathological hallmark of these age-related neurodegenerative diseases is the accumulation of specific proteins, including amyloid beta (Aβ), tau, α-synuclein (α-syn), TAR DNA-binding protein 43 (TDP43), and repeat-associated non-ATG (RAN) peptides, in the intra- and extracellular spaces of selected brain regions. Whereas it remains controversial whether these accumulations are pathogenic or merely a byproduct of disease, the majority of therapeutic research has focused on clearing protein aggregates. Immunotherapies have garnered particular attention for their ability to target specific protein strains and conformations as well as promote clearance. Immunotherapies can also be neuroprotective: by neutralizing extracellular protein aggregates, they reduce spread, synaptic damage, and neuroinflammation. This review will briefly examine the current state of research in immunotherapies against the 3 most commonly targeted proteins for age-related neurodegenerative disease: Aβ, tau, and α-syn. The discussion will then turn to combinatorial strategies that enhance the effects of immunotherapy against aggregating protein, followed by new potential targets of immunotherapy such as aging-related processes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00853-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-72229552020-05-15 Immunotherapies for Aging-Related Neurodegenerative Diseases—Emerging Perspectives and New Targets Kwon, Somin Iba, Michiyo Kim, Changyoun Masliah, Eliezer Neurotherapeutics Current Perspectives Neurological disorders such as Alzheimer’s disease (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD), and vascular dementia (VCID) have no disease-modifying treatments to date and now constitute a dementia crisis that affects 5 million in the USA and over 50 million worldwide. The most common pathological hallmark of these age-related neurodegenerative diseases is the accumulation of specific proteins, including amyloid beta (Aβ), tau, α-synuclein (α-syn), TAR DNA-binding protein 43 (TDP43), and repeat-associated non-ATG (RAN) peptides, in the intra- and extracellular spaces of selected brain regions. Whereas it remains controversial whether these accumulations are pathogenic or merely a byproduct of disease, the majority of therapeutic research has focused on clearing protein aggregates. Immunotherapies have garnered particular attention for their ability to target specific protein strains and conformations as well as promote clearance. Immunotherapies can also be neuroprotective: by neutralizing extracellular protein aggregates, they reduce spread, synaptic damage, and neuroinflammation. This review will briefly examine the current state of research in immunotherapies against the 3 most commonly targeted proteins for age-related neurodegenerative disease: Aβ, tau, and α-syn. The discussion will then turn to combinatorial strategies that enhance the effects of immunotherapy against aggregating protein, followed by new potential targets of immunotherapy such as aging-related processes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00853-2) contains supplementary material, which is available to authorized users. Springer International Publishing 2020-04-28 2020-07 /pmc/articles/PMC7222955/ /pubmed/32347461 http://dx.doi.org/10.1007/s13311-020-00853-2 Text en © This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020
spellingShingle Current Perspectives
Kwon, Somin
Iba, Michiyo
Kim, Changyoun
Masliah, Eliezer
Immunotherapies for Aging-Related Neurodegenerative Diseases—Emerging Perspectives and New Targets
title Immunotherapies for Aging-Related Neurodegenerative Diseases—Emerging Perspectives and New Targets
title_full Immunotherapies for Aging-Related Neurodegenerative Diseases—Emerging Perspectives and New Targets
title_fullStr Immunotherapies for Aging-Related Neurodegenerative Diseases—Emerging Perspectives and New Targets
title_full_unstemmed Immunotherapies for Aging-Related Neurodegenerative Diseases—Emerging Perspectives and New Targets
title_short Immunotherapies for Aging-Related Neurodegenerative Diseases—Emerging Perspectives and New Targets
title_sort immunotherapies for aging-related neurodegenerative diseases—emerging perspectives and new targets
topic Current Perspectives
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222955/
https://www.ncbi.nlm.nih.gov/pubmed/32347461
http://dx.doi.org/10.1007/s13311-020-00853-2
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AT masliaheliezer immunotherapiesforagingrelatedneurodegenerativediseasesemergingperspectivesandnewtargets