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Cellular and Molecular Life Sciences

, Volume 76, Issue 19, pp 3681–3694 | Cite as

Microglial priming of antigen presentation and adaptive stimulation in Alzheimer’s disease

  • Rashmi Das
  • Subashchandrabose ChinnathambiEmail author
Review

Abstract

The prominent pathological consequences of Alzheimer’s disease (AD) are the misfolding and mis-sorting of two cellular proteins, amyloid-β and microtubule-associated protein Tau. The accumulation of toxic phosphorylated Tau inside the neurons induces the increased processing of amyloid-β-associated signaling cascade and vice versa. Neuroinflammation-driven synaptic depletion and cognitive decline are substantiated by the cross talk of activated microglia and astroglia, leading to neuron degeneration. Microglia are the brain-resident immune effectors that prove their diverse functions in maintaining CNS homeostasis via collaboration with astrocytes and T lymphocytes. Age-related senescence and chronic inflammation activate microglia with increased pro-inflammatory markers, oxidative damage and phagocytosis. But the improper processing of misfolded protein via lysosomal pathway destines the spreading of ‘seed’ constituents to the nearby healthy neurons. Primed microglia process and present self-antigen such as amyloid-β and modified Tau to the infiltrated T lymphocytes through MHC I/II molecules. After an effective conversation with CD4+ T cells, microglial phenotype can be altered from pro-active M1 to neuro-protective M2 type, which corresponds to the tissue remodeling and homeostasis. In this review, we are focusing on the change in functionality of microglia from innate to adaptive immune response in the context of neuroprotection, which may help in the search of novel immune therapy in AD.

Keywords

Microglia Antigen presentation Neuroimmunomodulation T cell infiltration Immunotherapy Tauopathy Alzheimer’s disease 

Abbreviations

BACE1

Beta secretase 1

PTMs

Post-translational modifications

BBB

Blood–brain barrier

CNS

Central nervous system

ROS

Reactive oxygen species

NO

Nitric oxide

iNOS

Inorganic nitric oxide synthase

CD

Cluster of differentiation

MHC

Major histocompatibility complex

TGFβ

Transforming growth factor β

TNFα

Tumor necrosis factor α

IL

Interleukin

IFN

Interferon

TH

Helper T cell

Treg

Regulatory T cell

KO

Knockout

CR

Complement receptor

NFκB

Nuclear factor κ for B cell

mTOR

Mammalian target for rapamycin

Akt

Protein kinase B

ATP

Adenosine tri-phosphate

APC

Antigen-presenting cell

TREM2

Triggering receptor expressed on myeloid cells 2

ApoE

Apolipoprotein E

NFκB

Nuclear factor kappa-light-chain-enhancer of activated B cells

p38-MAPK

p38-mitogen-activated protein kinases

CSF1R

Colony-stimulating factor-1 receptor

Notes

Acknowledgements

This project is supported in part by grants from the Department of Biotechnology, Neuroscience Task Force (Medical Biotechnology-Human Development & Disease Biology DBT-HDDB)-BT/PR/15780/MED/122/4/2016 and in-house CSIR-National Chemical Laboratory Grant MLP029526. Special thanks to Ms. Nalini Gorantla, Mr. Abhishek Balmik and Ms. Shweta Sonawane for proofreading the manuscript. Rashmi Das acknowledges the fellowship from University Grant Commission (UGC) India.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Neurobiology Group, Division of Biochemical SciencesCSIR-National Chemical LaboratoryPuneIndia
  2. 2.Academy of Scientific and Innovative Research (AcSIR)PuneIndia

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