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August 27, 2026Expert Opinion on Therapeutic Targets

Targeting the NLRP3 inflammasome pathway associated with neuroinflammation mediated Alzheimer’s disease: pre-clinical and clinical status of emerging therapeutics

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Authors

ANAbul Kalam NajmiDYDevesh YaduvanshiRARishabh Aggarwal

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Overview

Narrative review highlights NLRP3 inflammasome inhibitors for neuroinflammation in Alzheimer's disease, suggesting nanoparticle delivery across the blood-brain barrier as a crucial strategy.

Key Points

  • To review the preclinical and clinical therapeutic landscape targeting the NLRP3 inflammasome pathway to mitigate neuroinflammation and disease progression in Alzheimer's disease.
  • Reviewed molecular cascades driven by neurotoxic microglial activation and NLRP3 inflammasome signaling.
  • Evaluated emerging therapeutic candidates, including bioactive phytochemicals, repurposed drugs, and novel synthetic inhibitors.
  • Assessed pharmacokinetic challenges related to drug delivery across the blood-brain barrier.
  • The NLRP3 inflammasome functions as a key molecular switch driving pro-inflammatory cytokine release (IL-1β, IL-18) and pyroptosis in Alzheimer's pathology.
  • Multiple bioactive and synthetic agents demonstrate preclinical efficacy in inhibiting the NLRP3 pathway, addressing root neuroinflammatory causes rather than superficial symptoms.
  • Overcoming the blood-brain barrier remains the primary translational barrier, requiring integration with advanced nanoparticle drug delivery platforms.

Cite This Study

Najmi et al. (2026) studied this question.

synapsesocial.com/papers/6a8fe99e10c91c1e926215e1https://doi.org/10.1080/14728222.2026.2723488
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