Targeting protein aggregation: the promising application of polyoxometalates in neurodegenerative diseases

Abstract

With the global aging trend, the incidence of neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), has greatly increased. NDDs are sporadic and rare inherited diseases of the nervous system characterized by loss of neurons and slow progressive degeneration in different regions of the nervous system. A common feature of many NDDs is the formation of persistent and irreversible protein aggregates during their pathogenesis, such as amyloid β (Aβ) and tau aggregates in AD, α-synuclein aggregates in PD and TDP-43 aggregates in ALS. Hence, therapeutic approaches aiming to inhibit the formation or promote the clearance of protein aggregates have emerged in recent years, some of which have advanced to clinical trials. Polyoxometalates (POMs), formed by the condensation reaction of early transition-metal oxo anions, are prime candidates for constructing functional nanoclusters covering a wide range of fields including catalysis, energy storage and biomedicine. A series of modified POMs obtained by high-throughput screening or rational design are able to modulate protein aggregation via stereoselectivity. Here we summarize and discuss recent progress in the therapeutic applications of POMs to target protein aggregation in NDDs.