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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http://dx.doi.org/10.1016/j.ejmech.2024.116684 | DOI Listing |
Mol Cell Biochem
January 2025
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via Luigi Vanvitelli 32, 20133, Milan, Italy.
Neurodegenerative diseases (NDs) are caused by progressive neuronal death and cognitive decline. Epigallocatechin 3-gallate (EGCG) is a polyphenolic molecule in green tea as a neuroprotective agent. This review evaluates the therapeutic effects of EGCG and explores the molecular mechanisms that show its neuroprotective properties.
View Article and Find Full Text PDFInt J Cancer
January 2025
Department of Neurosurgery, LMU University Hospital, Munich, Germany.
Neurologic immune-related adverse events (nirAEs) represent rare, yet severe side effects associated with immune checkpoint inhibitor (ICI) therapy. Given the absence of established diagnostic biomarkers for nirAEs, we aimed to evaluate the diagnostic utility of serum Neurofilament Light Chain (NfL) and Glial Fibrillary Acidic Protein (GFAP). Fifty-three patients were included at three comprehensive cancer centers, of these 20 patients with manifest nirAEs and 11 patients with irHypophysitis.
View Article and Find Full Text PDFZh Nevrol Psikhiatr Im S S Korsakova
January 2025
Pirogov Russian National Research Medical University (Pirogov University), Moscow, Russia.
Acute stroke is the second leading cause of death and the third leading cause of disability in the world. Ischemic stroke (IS) the most common type of stroke. In acute cerebral ischemia, damage to the brain tissue is complex and includes blood-brain barrier (BBB) dysfunction, neuroinflammation, oxidative stress, activation of intracellular and extracellular signaling pathways, expression of neurotoxic agents, excitotoxicity, and apoptosis.
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February 2025
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Baha University, Al-Baha 65779, Saudi Arabia.
Background: Microplastics are tiny plastic particles, typically less than 5 mm in size, formed from the breakdown of larger plastic products. This breakdown releases additives, including benzyl butyl phthalate (BBP), into the environment. Humans can be exposed to BBP through contaminated food and water, inhalation, and dermal contact.
View Article and Find Full Text PDFFood Funct
January 2025
College of Life Science, Sichuan Agricultural University, Yaan 625014, China.
β-Amyloid (Aβ) aggregation is the major pathological feature of Alzheimer's disease (AD), resulting in oxidative stress and further exacerbating Aβ aggregation. Ginger leaf polyphenols (GLP) have been found to possess antioxidant activity, evidencing their potential in addressing AD. GLP is mainly composed of 12 polyphenols, 8 organic acids, and 6 glycosides, of which polyphenols are predominantly composed of apigenin, kaempferol, and quercetin derivatives.
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