Anti-amyloid nanoclusters for the treatment of brain hazards associated with incurable neurodegenerative diseases

Neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD) have no cure and pose a serious threat to human health. The accumulated amyloid has been the therapeutic target of various studies for over a decade, but there is a lack of effective treatments due to various limitations, such as the difficulty to cross the blood-brain barrier (BBB) and unfavorable bioaccumulation. To over-come these challenges, ultra-small metal nanoclusters (MNCs) (<2 nm) have emerged as promising new agents. Simple modifications of MNCs efficiently cross the BBB to reach the brain and dissociate amyloid fibrils into less toxic species. In addition, the enzymatic behavior of MNCs facilitates the scavenging of intracellular reactive oxygen species (ROS) and alleviates neuroinflammation. Herein, we summarize the reported anti-amyloid MNCs. Multiple promising functions of MNCs that may alleviate the harms of neurodegenerative diseases are exhibited. The physicochemical properties that influence the inhibition and degradation of common amyloid fibrils, including alpha-synuclein (a -syn) and amyloid beta-peptide (AI3) are discussed. The prospect of optimizing MNCs to suppress more harm in the brain is presented to facilitate the development of practical therapies for neurodegenerative diseases. (c) 2022 Elsevier Ltd. All rights reserved.

Automated summary

Neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD) have no cure and pose a serious threat to human health. Ultra-small metal nanoclusters (MNCs) have emerged as promising agents for targeting accumulated amyloid in the brain, overcoming the limitations of crossing the blood-brain barrier and bioaccumulation. MNCs exhibit multiple functions, including dissociating amyloid fibrils and alleviating neuroinflammation, and have the potential for optimizing to develop practical therapies for neurodegenerative diseases.