Selective Inhibition of Tumor Necrosis Factor for Attenuating Alzheimer’s Disease: Strategies Targeting Neuroinflammation

TL;DR

This review explores how selectively blocking TNF-α, a key inflammatory molecule, could help treat Alzheimer’s disease by reducing harmful brain inflammation.

Contribution

The paper introduces targeted TNF-α inhibition as a novel therapeutic strategy for Alzheimer’s disease.

Findings

TNF-α activation worsens amyloid and tau pathology in Alzheimer’s disease.

Selective TNF-α inhibitors show promise in preclinical and clinical studies for regulating neuroinflammation.

Combining TNF-α inhibition with other approaches may offer a more effective treatment for Alzheimer’s.

Abstract

Neuroinflammation is increasingly recognized as a key feature in the development of Alzheimer’s disease (AD), with tumor necrosis factor-alpha (TNF-α) playing a crucial role in initiating inflammatory responses. Continuous activation of TNF-α leads to synaptic dysfunction, neuronal loss, and worsening of amyloid and tau pathology. Specifically, the upregulation of the pro-inflammatory cytokine TNF-α in the brain activates its receptors (TNFR1 & TNFR2). Targeting TNF-α through selective inhibition presents a promising therapeutic strategy for regulating neuroinflammatory responses without compromising systemic immunity. This review discusses current insights into TNF-α signaling in AD progression and examines the effectiveness of selective TNF-α inhibitors in preclinical and clinical studies. We also highlighted specific TNF-α inhibitors, including small molecules and gene therapy approaches, for chronic inflammatory conditions and discussed the limitations and future directions of the current review. Targeted TNF-α inhibition could serve as a novel, disease-modifying treatment for AD, especially when combined with multi-targeted approaches addressing amyloid burden, tau pathology, oxidative stress, and neuroinflammation.

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