Adaptive immune regulation of glial homeostasis as an immunization strategy for neurodegenerative diseases.
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.
Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Lisa M
LM
Kosloski
Duy M
DM
Ha
Jessica A L
JA
Hutter
David K
DK
Stone
Michael R
MR
Pichler
Ashley D
AD
Reynolds
Howard E
HE
Gendelman
R Lee
RL
Mosley
D056704:Adaptive Immunity; D000818:Animals; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D009457:Neuroglia / Q000166:cytology / Q000276:immunology* / Q000473:pathology