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Inflammation and the Pathophysiology of Astrocytes in Neurodegenerative Diseases

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Neuroinflammation and Neurodegeneration

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Abstract

Astrocytes, the most abundant cell in the central nervous system, are essential for brain function and homeostasis. This chapter focuses on the immunological role of astrocytes in the pathology of major neurodegenerative diseases. Astrocyte activation, or astrogliosis, has been observed in many neurodegenerative diseases. Factors associated with neurodegeneration including extracellular oligomerized proteins such as amyloid β and α-synuclein as well as inflammatory cytokines and chemokines can influence the functionality of astrocytes. In response to such stimuli, astrocytes produce a multitude of soluble factors including cytokines, chemokines, reactive oxygen/nitrogen species, and growth factors. This astrocytic response is initially protective, limiting damage and promoting functional recovery. However, the prolonged and progressive nature of neurodegenerative diseases establishes an environment in which astrogliosis may be aberrantly sustained, and the ongoing production of astrocyte-derived molecules contributes to the non-resolving inflammatory and neurotoxic landscape associated with neurodegeneration.

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Abbreviations

6-OHDA:

6-hydroxydopamine

AD:

Alzheimer’s disease

ALS:

Amyotrophic lateral sclerosis

Aβ:

Amyloid β

BBB:

Blood–brain barrier

BDNF:

Brain-derived neurotrophic factor

CNS:

Central nervous system

DAMP:

Damage-associated molecular pattern

GDNF:

Glial-derived neurotrophic factor

GFAP:

Glial fibrillary acidic protein

HD:

Huntington’s disease

IFN:

Interferon

ISG:

Interferon-stimulated genes

MHC:

Major histocompatibility complex

MMP:

Matrix metalloproteinase

MPTP:

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

MS:

Multiple sclerosis

NFT:

Neurofibrillary tangles

NF-κB:

Nuclear factor-kappa B

NOD:

Nucleotide-binding oligomerization domain

PGD2:

Prostaglandin D2

PRR:

Pattern recognition receptor

STAT:

Signal transducer and activator of transcription

SN:

Substantia nigra

SOD1:

Superoxide dismutase 1

TBI:

Traumatic brain injury

Th:

T helper

TLR:

Toll-like receptor

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Acknowledgments

This work was supported in part by grants from the National Multiple Sclerosis Society (NMSS), CA-1059A-13 and RG-4885-A-14 to E.N.B. and TA-3050-A-1 to G.P.M., and NIH grants NS45290 and NS57563 (E.N.B.).

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Authors and Affiliations

  1. Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, 1918 University Boulevard, MCLM 388, Birmingham, AL, 35294-0006, USA

    Gordon P. Meares Ph.D.

  2. Department of Cell, Developmental and Integrative Biology, 1900 University Boulevard, THT 926A, Birmingham, AL, 35294-0006, USA

    Etty N. Benveniste Ph.D.

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  1. Gordon P. Meares Ph.D.
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Correspondence to Gordon P. Meares Ph.D. .

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  1. Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA

    Phillip K. Peterson

  2. Department of Biochemistry Department of Molecular Biology, University of Miami School of Medicine, Miami, Florida, USA

    Michal Toborek

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Meares, G.P., Benveniste, E.N. (2014). Inflammation and the Pathophysiology of Astrocytes in Neurodegenerative Diseases. In: Peterson, P., Toborek, M. (eds) Neuroinflammation and Neurodegeneration. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1071-7_4

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