Immunotherapies for movement disorders: Parkinson’S disease and amyotrophic lateral sclerosis

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Although patterns of neuronal degeneration are unique in PD and ALS, both disorders share common pathways and processes that support and possibly initiate neurodegeneration. Most of these processes are associated with induction, propagation, or consequences of neuroinflammation. Increased numbers of microglia that express reactive phenotypes and proximate dying neurons reflect the neuroinflammatory cellular response. Neuroinflammation amplifies oxidative stresses via reactive oxygen, nitrogen, and carbon species that react with biomolecules and increase molecular modifications of lipids, proteins, and nucleic acids. These reactive modifications eventually become deleterious to biochemical and cellular processes resulting in dysregulation of cellular functions and further neuronal injury and death. Whether neuroinflammatory responses are causal or consequential remains to be determined. Nevertheless, the importance of inflammatory responses to neurodegeneration is underscored in animal models, whereby attenuation of neuroinflammation by genetic manipulation or pharmacological agents mitigates neurodegeneration and increases neuronal survival. As such, immunological strategies that target neuroinflammatory processes represent promising candidates for therapeutic intervention in neurodegenerative disorders. These strategies embrace the capacity of regulatory T cells to protect neurons either directly via neurotrophic factors, or indirectly by modulation of microglial function to attenuate neuroinflammatory responses and by induction of astrocyte-derived neurotrophic factors.

Original languageEnglish (US)
Title of host publicationNeuroimmune Pharmacology
PublisherSpringer International Publishing
Pages767-797
Number of pages31
ISBN (Electronic)9783319440224
ISBN (Print)9783319440200
DOIs
StatePublished - Jan 1 2016

Fingerprint

Nerve Growth Factors
Movement Disorders
Amyotrophic Lateral Sclerosis
Immunotherapy
Parkinson Disease
Biochemical Phenomena
Neurons
Microglia
Regulatory T-Lymphocytes
Astrocytes
Neurodegenerative Diseases
Nucleic Acids
Oxidative Stress
Nitrogen
Carbon
Animal Models
Pharmacology
Oxygen
Phenotype
Lipids

Keywords

  • Dopaminergic neurons
  • Glatiramer acetate
  • MPTP
  • Macrophage
  • Microglia
  • Nadph oxidase
  • Peripheral benzodiazepine receptors
  • SNpc
  • SOD1
  • Striatum
  • T lymphocyte or T cell
  • TDP-43
  • pk11195
  • α-synuclein

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Immunotherapies for movement disorders : Parkinson’S disease and amyotrophic lateral sclerosis. / Schutt, Charles; Gendelman, Howard Eliot; Mosley, R Lee.

Neuroimmune Pharmacology. Springer International Publishing, 2016. p. 767-797.

Research output: Chapter in Book/Report/Conference proceedingChapter

Schutt, Charles ; Gendelman, Howard Eliot ; Mosley, R Lee. / Immunotherapies for movement disorders : Parkinson’S disease and amyotrophic lateral sclerosis. Neuroimmune Pharmacology. Springer International Publishing, 2016. pp. 767-797
@inbook{fb79a4d13e154b3bbe1166afbe5a3d0d,
title = "Immunotherapies for movement disorders: Parkinson’S disease and amyotrophic lateral sclerosis",
abstract = "Although patterns of neuronal degeneration are unique in PD and ALS, both disorders share common pathways and processes that support and possibly initiate neurodegeneration. Most of these processes are associated with induction, propagation, or consequences of neuroinflammation. Increased numbers of microglia that express reactive phenotypes and proximate dying neurons reflect the neuroinflammatory cellular response. Neuroinflammation amplifies oxidative stresses via reactive oxygen, nitrogen, and carbon species that react with biomolecules and increase molecular modifications of lipids, proteins, and nucleic acids. These reactive modifications eventually become deleterious to biochemical and cellular processes resulting in dysregulation of cellular functions and further neuronal injury and death. Whether neuroinflammatory responses are causal or consequential remains to be determined. Nevertheless, the importance of inflammatory responses to neurodegeneration is underscored in animal models, whereby attenuation of neuroinflammation by genetic manipulation or pharmacological agents mitigates neurodegeneration and increases neuronal survival. As such, immunological strategies that target neuroinflammatory processes represent promising candidates for therapeutic intervention in neurodegenerative disorders. These strategies embrace the capacity of regulatory T cells to protect neurons either directly via neurotrophic factors, or indirectly by modulation of microglial function to attenuate neuroinflammatory responses and by induction of astrocyte-derived neurotrophic factors.",
keywords = "Dopaminergic neurons, Glatiramer acetate, MPTP, Macrophage, Microglia, Nadph oxidase, Peripheral benzodiazepine receptors, SNpc, SOD1, Striatum, T lymphocyte or T cell, TDP-43, pk11195, α-synuclein",
author = "Charles Schutt and Gendelman, {Howard Eliot} and Mosley, {R Lee}",
year = "2016",
month = "1",
day = "1",
doi = "10.1007/978-3-319-44022-4_46",
language = "English (US)",
isbn = "9783319440200",
pages = "767--797",
booktitle = "Neuroimmune Pharmacology",
publisher = "Springer International Publishing",

}

TY - CHAP

T1 - Immunotherapies for movement disorders

T2 - Parkinson’S disease and amyotrophic lateral sclerosis

AU - Schutt, Charles

AU - Gendelman, Howard Eliot

AU - Mosley, R Lee

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Although patterns of neuronal degeneration are unique in PD and ALS, both disorders share common pathways and processes that support and possibly initiate neurodegeneration. Most of these processes are associated with induction, propagation, or consequences of neuroinflammation. Increased numbers of microglia that express reactive phenotypes and proximate dying neurons reflect the neuroinflammatory cellular response. Neuroinflammation amplifies oxidative stresses via reactive oxygen, nitrogen, and carbon species that react with biomolecules and increase molecular modifications of lipids, proteins, and nucleic acids. These reactive modifications eventually become deleterious to biochemical and cellular processes resulting in dysregulation of cellular functions and further neuronal injury and death. Whether neuroinflammatory responses are causal or consequential remains to be determined. Nevertheless, the importance of inflammatory responses to neurodegeneration is underscored in animal models, whereby attenuation of neuroinflammation by genetic manipulation or pharmacological agents mitigates neurodegeneration and increases neuronal survival. As such, immunological strategies that target neuroinflammatory processes represent promising candidates for therapeutic intervention in neurodegenerative disorders. These strategies embrace the capacity of regulatory T cells to protect neurons either directly via neurotrophic factors, or indirectly by modulation of microglial function to attenuate neuroinflammatory responses and by induction of astrocyte-derived neurotrophic factors.

AB - Although patterns of neuronal degeneration are unique in PD and ALS, both disorders share common pathways and processes that support and possibly initiate neurodegeneration. Most of these processes are associated with induction, propagation, or consequences of neuroinflammation. Increased numbers of microglia that express reactive phenotypes and proximate dying neurons reflect the neuroinflammatory cellular response. Neuroinflammation amplifies oxidative stresses via reactive oxygen, nitrogen, and carbon species that react with biomolecules and increase molecular modifications of lipids, proteins, and nucleic acids. These reactive modifications eventually become deleterious to biochemical and cellular processes resulting in dysregulation of cellular functions and further neuronal injury and death. Whether neuroinflammatory responses are causal or consequential remains to be determined. Nevertheless, the importance of inflammatory responses to neurodegeneration is underscored in animal models, whereby attenuation of neuroinflammation by genetic manipulation or pharmacological agents mitigates neurodegeneration and increases neuronal survival. As such, immunological strategies that target neuroinflammatory processes represent promising candidates for therapeutic intervention in neurodegenerative disorders. These strategies embrace the capacity of regulatory T cells to protect neurons either directly via neurotrophic factors, or indirectly by modulation of microglial function to attenuate neuroinflammatory responses and by induction of astrocyte-derived neurotrophic factors.

KW - Dopaminergic neurons

KW - Glatiramer acetate

KW - MPTP

KW - Macrophage

KW - Microglia

KW - Nadph oxidase

KW - Peripheral benzodiazepine receptors

KW - SNpc

KW - SOD1

KW - Striatum

KW - T lymphocyte or T cell

KW - TDP-43

KW - pk11195

KW - α-synuclein

UR - http://www.scopus.com/inward/record.url?scp=85045978221&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045978221&partnerID=8YFLogxK

U2 - 10.1007/978-3-319-44022-4_46

DO - 10.1007/978-3-319-44022-4_46

M3 - Chapter

AN - SCOPUS:85045978221

SN - 9783319440200

SP - 767

EP - 797

BT - Neuroimmune Pharmacology

PB - Springer International Publishing

ER -