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Activation of microglia and astrocytes: a roadway to neuroinflammation and Alzheimer’s disease

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Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease that is of high importance to the neuroscience world, yet the complex pathogenicity is not fully understood. Inflammation is usually observed in AD and could implicate both beneficial or detrimental effects depending on the severity of the disease. During initial AD pathology, microglia and astrocyte activation is beneficial since they are involved in amyloid-beta clearance. However, with the progression of the disease, activated microglia elicit detrimental effects by the overexpression of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) bringing forth neurodegeneration in the surrounding brain regions. This results in decline in Aβ clearance by microglia; Aβ accumulation thus increases in the brain resulting in neuroinflammation. Thus, Aβ accumulation is the effect of increased release of pro-inflammatory molecules. Reactive astrocytes acquire gain of toxic function and exhibits neurotoxic effects with loss of neurotrophic functions. Astrocyte dysfunctioning results in increased release of cytokines and inflammatory mediators, neurodegeneration, decreased glutamate uptake, loss of neuronal synapses, and ultimately cognitive deficits in AD. We discuss the role of intracellular signaling pathways in the inflammatory responses produced by astrocytes and microglial activation, including the glycogen synthase kinase-3β, nuclear factor kappa B cascade, mitogen-activated protein kinase pathways and c-Jun N-terminal kinase. In this review, we describe the role of neuroinflammation in the chronicity of AD pathogenesis and an overview of the recent research towards the development of new therapies to treat this disorder.

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Acknowledgements

Authors are thankful to the Science and Engineering Board (SERB), Department of Science and Technology, Govt. of India, New Delhi, for providing financial assistance under Fast Track Scheme (DST: SB/YS/LS-111/2013) to Dr. Rahul Deshmukh.

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  1. Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda, Punjab, 151001, India

    Darshpreet Kaur & Rahul Deshmukh

  2. Government College of Pharmacy, Rohru, Shimla, Himachal Pradesh, 171207, India

    Vivek Sharma

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Kaur, D., Sharma, V. & Deshmukh, R. Activation of microglia and astrocytes: a roadway to neuroinflammation and Alzheimer’s disease. Inflammopharmacol 27, 663–677 (2019). https://doi.org/10.1007/s10787-019-00580-x

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