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Updated: Oct 1, 2025

Improved 3D Hydrogel Cultures of Primary Glial Cells for In Vitro Modelling of Neuroinflammation
Published on: December 8, 2017
Role of chronic neuroinflammation in neuroplasticity and cognitive function: A hypothesis
Daniela Lecca1, Yoo Jin Jung1,2, Michael T Scerba1
1Drug Design & Development Section, Translational Gerontology Branch, Intramural Research Program National Institute on Aging, NIH, Baltimore, Maryland, USA.
Objective:
Evaluating the efficacy of 3,6'-dithioPomalidomide in 5xFAD Alzheimer's disease (AD) mice to test the hypothesis that neuroinflammation is directly involved in the development of synaptic/neuronal loss and cognitive decline.
Background:
Amyloid-β (Aβ) or tau-focused clinical trials have proved unsuccessful in mitigating AD-associated cognitive impairment. Identification of new drug targets is needed. Neuroinflammation is a therapeutic target in neurodegenerative disorders, and TNF-α a pivotal neuroinflammatory driver.
New Hypothesis:
AD-associated chronic neuroinflammation directly drives progressive synaptic/neuronal loss and cognitive decline. Pharmacologically mitigating microglial/astrocyte activation without altering Aβ generation will define the role of neuroinflammation in AD progression.
Major Challenges:
Difficulty of TNF-α-lowering compounds reaching brain, and identification of a therapeutic-time window to preserve the beneficial role of neuroinflammatory processes.
Linkage To Other Major Theories:
Microglia/astroglia are heavily implicated in maintenance of synaptic plasticity/function in healthy brain and are disrupted by Aβ. Mitigation of chronic gliosis can restore synaptic homeostasis/cognitive function.
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