AI Article Synopsis

  • - Alzheimer's disease (AD) is a serious global health challenge with no cure, marked by brain degeneration and cognitive decline; current treatments mainly manage symptoms rather than modify the disease itself.
  • - The accumulation of amyloid-β (Aβ) peptides plays a key role in AD pathology, and there's a shift in focus from targeting mature amyloid fibrils to addressing more toxic soluble Aβ oligomers that damage nerve cells and synapses.
  • - Natural products show promise in combating Aβ oligomer neurotoxicity through various strategies, suggesting they could lead to new, effective treatments for AD by understanding how they influence Aβ oligomer behavior in different experimental settings.

Article Abstract

Alzheimer's disease (AD) constitutes a major global health issue, characterized by progressive neurodegeneration and cognitive impairment, for which no curative treatment is currently available. Current therapeutic approaches are focused on symptom management, highlighting the critical need for disease-modifying therapy. The hallmark pathology of AD involves the aggregation and accumulation of amyloid-β (Aβ) peptides in the brain. Consequently, drug discovery efforts in recent decades have centered on the Aβ aggregation cascade, which includes the transition of monomeric Aβ peptides into toxic oligomers and, ultimately, mature fibrils. Historically, anti-Aβ strategies focused on the clearance of amyloid fibrils using monoclonal antibodies. However, substantial evidence has highlighted the critical role of Aβ oligomers (AβOs) in AD pathogenesis. Soluble AβOs are now recognized as more toxic than fibrils, directly contributing to synaptic impairment, neuronal damage, and the onset of AD. Targeting AβOs has emerged as a promising therapeutic approach to mitigate cognitive decline in AD. Natural products (NPs) have demonstrated promise against AβO neurotoxicity through various mechanisms, including preventing AβO formation, enhancing clearance mechanisms, or converting AβOs into non-toxic species. Understanding the mechanisms by which anti-AβO NPs operate is useful for developing disease-modifying treatments for AD. In this review, we explore the role of NPs in mitigating AβO neurotoxicity for AD drug discovery, summarizing key evidence from biophysical methods, cellular assays, and animal models. By discussing how NPs modulate AβO neurotoxicity across various experimental systems, we aim to provide valuable insights into novel therapeutic strategies targeting AβOs in AD.

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Source
http://dx.doi.org/10.1016/j.ejmech.2024.116684DOI Listing

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