Control of neuroinflammation as a therapeutic strategy for amyotrophic lateral sclerosis and other neurodegenerative disorders

Research output: Contribution to journalComment/debate

20 Citations (Scopus)

Abstract

Neurodegenerative diseases, Alzheimer's and Parkinson's diseases, and amyotrophic lateral sclerosis (ALS) are progressive and devastating disorders of the nervous system without cure. Although a number of distinct, but not mutually exclusive, mechanisms can affect disease pathogenesis, neuroinflammation stands in common. Neuroinflammatory responses occur as a consequence of oxidative and excitotoxic neuronal damage, mitochondrial dysfunction, and protein aggregation. Thus, it is believed drugs that modulate inflammation may combat disease progression. Such strategies include those commented on in the report by Arie Neymotin et al. demonstrating lenalidomide's anti-inflammatory and neuroprotective responses in the G93A mutant superoxide dismutase-1 mouse model of ALS (Neymotin et al., 2009). While anti-inflammatory interventions may be required, they may not be sufficient to positively affect clinical outcomes. The targeting of combinations of pathogenic events including clearance of disaggregated proteins together with neuroprotective and immune modulatory strategies may all be required to facilitate positive therapeutic outcomes. This may include the targeting of both innate and adaptive neurotoxic immune responses. This commentary is designed to summarize the promises and perils in achieving immunoregulation for brain homeostatic responses and inevitable therapeutic gain. Promising new ways to optimize immunization schemes and measure their clinical efficacy are discussed with a particular focus on ALS.

Original languageEnglish (US)
Pages (from-to)1-5
Number of pages5
JournalExperimental Neurology
Volume222
Issue number1
DOIs
StatePublished - Mar 1 2010

Fingerprint

Amyotrophic Lateral Sclerosis
Neurodegenerative Diseases
Anti-Inflammatory Agents
Mitochondrial Proteins
Adaptive Immunity
Nervous System Diseases
Parkinson Disease
Disease Progression
Immunization
Alzheimer Disease
Therapeutics
Inflammation
Brain
Pharmaceutical Preparations
Proteins

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

@article{9a5ac1ddf93c4beb86c9de8128fb1a9e,
title = "Control of neuroinflammation as a therapeutic strategy for amyotrophic lateral sclerosis and other neurodegenerative disorders",
abstract = "Neurodegenerative diseases, Alzheimer's and Parkinson's diseases, and amyotrophic lateral sclerosis (ALS) are progressive and devastating disorders of the nervous system without cure. Although a number of distinct, but not mutually exclusive, mechanisms can affect disease pathogenesis, neuroinflammation stands in common. Neuroinflammatory responses occur as a consequence of oxidative and excitotoxic neuronal damage, mitochondrial dysfunction, and protein aggregation. Thus, it is believed drugs that modulate inflammation may combat disease progression. Such strategies include those commented on in the report by Arie Neymotin et al. demonstrating lenalidomide's anti-inflammatory and neuroprotective responses in the G93A mutant superoxide dismutase-1 mouse model of ALS (Neymotin et al., 2009). While anti-inflammatory interventions may be required, they may not be sufficient to positively affect clinical outcomes. The targeting of combinations of pathogenic events including clearance of disaggregated proteins together with neuroprotective and immune modulatory strategies may all be required to facilitate positive therapeutic outcomes. This may include the targeting of both innate and adaptive neurotoxic immune responses. This commentary is designed to summarize the promises and perils in achieving immunoregulation for brain homeostatic responses and inevitable therapeutic gain. Promising new ways to optimize immunization schemes and measure their clinical efficacy are discussed with a particular focus on ALS.",
author = "Mosley, {R Lee} and Gendelman, {Howard Eliot}",
year = "2010",
month = "3",
day = "1",
doi = "10.1016/j.expneurol.2009.12.018",
language = "English (US)",
volume = "222",
pages = "1--5",
journal = "Experimental Neurology",
issn = "0014-4886",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Control of neuroinflammation as a therapeutic strategy for amyotrophic lateral sclerosis and other neurodegenerative disorders

AU - Mosley, R Lee

AU - Gendelman, Howard Eliot

PY - 2010/3/1

Y1 - 2010/3/1

N2 - Neurodegenerative diseases, Alzheimer's and Parkinson's diseases, and amyotrophic lateral sclerosis (ALS) are progressive and devastating disorders of the nervous system without cure. Although a number of distinct, but not mutually exclusive, mechanisms can affect disease pathogenesis, neuroinflammation stands in common. Neuroinflammatory responses occur as a consequence of oxidative and excitotoxic neuronal damage, mitochondrial dysfunction, and protein aggregation. Thus, it is believed drugs that modulate inflammation may combat disease progression. Such strategies include those commented on in the report by Arie Neymotin et al. demonstrating lenalidomide's anti-inflammatory and neuroprotective responses in the G93A mutant superoxide dismutase-1 mouse model of ALS (Neymotin et al., 2009). While anti-inflammatory interventions may be required, they may not be sufficient to positively affect clinical outcomes. The targeting of combinations of pathogenic events including clearance of disaggregated proteins together with neuroprotective and immune modulatory strategies may all be required to facilitate positive therapeutic outcomes. This may include the targeting of both innate and adaptive neurotoxic immune responses. This commentary is designed to summarize the promises and perils in achieving immunoregulation for brain homeostatic responses and inevitable therapeutic gain. Promising new ways to optimize immunization schemes and measure their clinical efficacy are discussed with a particular focus on ALS.

AB - Neurodegenerative diseases, Alzheimer's and Parkinson's diseases, and amyotrophic lateral sclerosis (ALS) are progressive and devastating disorders of the nervous system without cure. Although a number of distinct, but not mutually exclusive, mechanisms can affect disease pathogenesis, neuroinflammation stands in common. Neuroinflammatory responses occur as a consequence of oxidative and excitotoxic neuronal damage, mitochondrial dysfunction, and protein aggregation. Thus, it is believed drugs that modulate inflammation may combat disease progression. Such strategies include those commented on in the report by Arie Neymotin et al. demonstrating lenalidomide's anti-inflammatory and neuroprotective responses in the G93A mutant superoxide dismutase-1 mouse model of ALS (Neymotin et al., 2009). While anti-inflammatory interventions may be required, they may not be sufficient to positively affect clinical outcomes. The targeting of combinations of pathogenic events including clearance of disaggregated proteins together with neuroprotective and immune modulatory strategies may all be required to facilitate positive therapeutic outcomes. This may include the targeting of both innate and adaptive neurotoxic immune responses. This commentary is designed to summarize the promises and perils in achieving immunoregulation for brain homeostatic responses and inevitable therapeutic gain. Promising new ways to optimize immunization schemes and measure their clinical efficacy are discussed with a particular focus on ALS.

UR - http://www.scopus.com/inward/record.url?scp=77649337966&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77649337966&partnerID=8YFLogxK

U2 - 10.1016/j.expneurol.2009.12.018

DO - 10.1016/j.expneurol.2009.12.018

M3 - Comment/debate

VL - 222

SP - 1

EP - 5

JO - Experimental Neurology

JF - Experimental Neurology

SN - 0014-4886

IS - 1

ER -