Current Alzheimer Research

Debomoy K. Lahiri  
Department of Psychiatry, Indiana University School of Medicine
Neuroscience Research Center
Indianapolis, IN 46202
USA

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Astrocytes: Implications for Neuroinflammatory Pathogenesis of Alzheimers Disease

Author(s): Chuanyu Li, Rui Zhao, Kai Gao, Zheng Wei, Michael Yaoyao Yin, Lok Ting Lau, Dehua Chui, Albert Cheung Hoi Yu.

Abstract:

Alzheimers disease (AD) is a neurodegenerative disease with major clinical hallmarks of memory loss, dementia, and cognitive impairment. Neuroinflammation is involved in the onset of several neurodegenerative disorders. Astrocyte is the most abundant type of glial cells in the central nervous system (CNS) and appears to be involved in the induction of neuroinflammation. Under stress and injury, astrocytes become astrogliotic leading to an upregulation of the expression of proinflammatory cytokines and chemokines, which are associated with the pathogenesis of AD. Cytokines and related molecules play roles in both neuroprotection and neurodegeneration in the CNS. During early AD pathogenesis, amyloid beta (Aβ), S100B and IL-1β could bring about a vicious cycle of Aβ generation between astrocytes and neurons leading to chronic, sustained and progressive neuroinflammation. In advanced stages of AD, TRAIL secreted from astrocytes have been shown to bind to death receptor 5 (DR5) on neurons to trigger apoptosis in a caspase-8-dependent manner. Furthermore, astrocytes could be reactivated by TGFβ1 to generate more Aβ and to undergo the aggravating astrogliosis. TGFβ2 was also observed to cooperate with Aβ to cause neuronal demise by destroying the stability of lysosomes in neurons. Inflammatory molecules can be either potential biomarkers for diagnosis or target molecules for therapeutic intervention. Understanding their roles and their relationship with activated astrocytes is particularly important for attenuating neuroinflammation in the early stage of AD. The main purpose of this review is to provide a comprehensive insight into the role of astrocytes in the neuroinflammatory pathogenesis of AD.

Keywords: Alzheimer's disease, astrocyte, inflammation, cytokine, chemokine, amyloid beta, death receptor, TRAIL, Amyloid precursor protein, alpha secretase, IP-10, MCP-1, S100B, microglia

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Article Details

VOLUME: 8
ISSUE: 1
Year: 2011
Page: [67 - 80]
Pages: 14
DOI: 10.2174/156720511794604543