Liquid-liquid phase separation of α-synuclein is highly sensitive to sequence complexity.

The Parkinson's-associated protein α-synuclein (α-syn) can undergo liquid-liquid phase separation (LLPS), which typically leads to the formation of amyloid fibrils. The coincidence of LLPS and amyloid formation has complicated the identification of the molecular determinants unique to LLPS of α-syn. Moreover, the lack of strategies to selectively perturb LLPS makes it difficult to dissect the biological roles specific to α-syn LLPS, independent of fibrillation.

Liquid-liquid phase separation of α-synuclein is highly sensitive to sequence complexity.

The Parkinson's-associated protein α-synuclein (α-syn) can undergo liquid-liquid phase separation (LLPS), which typically leads to the formation of amyloid fibrils. The coincidence of LLPS and amyloid formation has complicated the identification of the molecular determinants unique to LLPS of α-syn. Moreover, the lack of strategies to selectively perturb LLPS makes it difficult to dissect the biological roles specific to α-syn LLPS, independent of fibrillation.

Cholesterol in Synaptic Vesicle Membranes Regulates the Vesicle-Binding, Function, and Aggregation of α-Synuclein.

Loss of function and aggregation of the neuronal protein α-Synuclein (A-Syn) underlies the pathogenesis of Parkinson's disease (PD), and both the function and aggregation of this protein happen to be mediated via its binding to the synaptic vesicles (SVs) at the presynaptic termini. An essential constituent of SV membranes is cholesterol, with which A-Syn directly interacts while binding to membranes. Thus, cholesterol content in SV membranes is likely to affect the binding of A-Syn to these vesicles and consequently its functional and pathogenic behaviors.

Modulation of α-Synuclein Fibrillation by Ultrasmall and Biocompatible Gold Nanoclusters.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, the pathogenesis of which is closely linked to the misfolding and aggregation of the neuronal protein α-Synuclein (A-Syn). Numerous molecules that inhibit/modulate the pathogenic aggregation of A-Syn in an effort to tackle PD pathogenesis have been reported, but none so far have been successful in treating the disease at the clinic. One major reason for this is the poor blood-brain barrier (BBB) permeability of most of the molecules being used.

An aminoglycoside antibiotic inhibits both lipid-induced and solution-phase fibrillation of α-synuclein in vitro.

Parkinson's disease (PD), closely associated with the misfolding and aggregation of the neuronal protein α-synuclein (A-Syn), is a neurodegenerative disorder with no cure to date. Here, we show that the commercially available, inexpensive, aminoglycoside antibiotic kanamycin effectively inhibits both lipid-induced and solution-phase aggregation of A-Syn in vitro, pointing towards the prospective repurposing of kanamycin as a potential anti-PD drug.

Modulation of α-Synuclein Aggregation by Cytochrome c Binding and Hetero-dityrosine Adduct Formation.

The aggregation of α-synuclein (α-Syn) has been implicated strongly in Parkinson's disease (PD). The intrinsically disordered nature of α-Syn makes this protein prone to self-association or heteroassociation with another protein or lipid. While conformational fluctuation and free radical chemistry have been shown to play important roles in its ability toward self- and heteroassociation, any systematic understanding of their contributions is missing.