Adaptive immune regulation of glial homeostasis as an immunization strategy for neurodegenerative diseases

Lisa M. Kosloski, Duy M. Ha, Jessica A L Hutter, David K. Stone, Michael R Pichler, Ashley D. Reynolds, Howard Eliot Gendelman, R Lee Mosley

Research output: Contribution to journalReview article

27 Citations (Scopus)

Abstract

Neurodegenerative diseases, notably Alzheimer's and Parkinson's diseases, are amongst the most devastating disorders afflicting the elderly. Currently, no curative treatments or treatments that interdict disease progression exist. Over the past decade, immunization strategies have been proposed to combat disease progression. Such strategies induce humoral immune responses against misfolded protein aggregates to facilitate their clearance. Robust adaptive immunity against misfolded proteins, however, accelerates disease progression, precipitated by induced effector T cell responses that lead to encephalitis and neuronal death. Since then, mechanisms that attenuate such adaptive neurotoxic immune responses have been sought. We propose that shifting the balance between effector and regulatory T cell activity can attenuate neurotoxic inflammatory events. This review summarizes advances in immune regulation to achieve a homeostatic glial response for therapeutic gain. Promising new ways to optimize immunization schemes and measure their clinical efficacy are also discussed.

Original languageEnglish (US)
Pages (from-to)1261-1276
Number of pages16
JournalJournal of Neurochemistry
Volume114
Issue number5
DOIs
StatePublished - Sep 1 2010

Fingerprint

Neurodegenerative diseases
Immunization
Neuroglia
Neurodegenerative Diseases
Disease Progression
Homeostasis
Adaptive Immunity
T-cells
Regulatory T-Lymphocytes
Encephalitis
Humoral Immunity
Parkinson Disease
Alzheimer Disease
Therapeutics
T-Lymphocytes
Proteins

Keywords

  • Parkinson's disease
  • immunization
  • inflammation
  • microglia
  • neuroprotection
  • regulatory T cells
  • therapeutic vaccination

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Adaptive immune regulation of glial homeostasis as an immunization strategy for neurodegenerative diseases. / Kosloski, Lisa M.; Ha, Duy M.; Hutter, Jessica A L; Stone, David K.; Pichler, Michael R; Reynolds, Ashley D.; Gendelman, Howard Eliot; Mosley, R Lee.

In: Journal of Neurochemistry, Vol. 114, No. 5, 01.09.2010, p. 1261-1276.

Research output: Contribution to journalReview article

Kosloski, Lisa M. ; Ha, Duy M. ; Hutter, Jessica A L ; Stone, David K. ; Pichler, Michael R ; Reynolds, Ashley D. ; Gendelman, Howard Eliot ; Mosley, R Lee. / Adaptive immune regulation of glial homeostasis as an immunization strategy for neurodegenerative diseases. In: Journal of Neurochemistry. 2010 ; Vol. 114, No. 5. pp. 1261-1276.
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