Distinct regulation of Tau Monomer and aggregate uptake and intracellular accumulation in human neurons.

Background: The prion-like spreading of Tau pathology is the leading cause of disease progression in various tauopathies. A critical step in propagating pathologic Tau in the brain is the transport from the extracellular environment and accumulation inside naïve neurons. Current research indicates that human neurons internalize both the physiological extracellular Tau (eTau) monomers and the pathological eTau aggregates.

The status of the terminal regions of α-synuclein in different forms of aggregates during fibrillization.

The α-synuclein (αSN) amyloid fibrillization process is known to be a crucial phenomenon associated with neuronal loss in various neurodegenerative diseases, most famously Parkinson's disease. The process involves different aggregated species and ultimately leads to formation of β-sheet rich fibrillar structures. Despite the essential role of αSN aggregation in the pathoetiology of various neurological disorders, the characteristics of various assemblies are not fully understood.

In vitro models of synucleinopathies: informing on molecular mechanisms and protective strategies.

Alpha-synuclein (α-Syn) is a central player in Parkinson's disease (PD) and in a spectrum of neurodegenerative diseases collectively known as synucleinopathies. The protein was first associated with PD just over 20 years ago, when it was found to (i) be a major component of Lewy bodies and (ii) to be also associated with familial forms of PD. The characterization of α-Syn pathology has been achieved through postmortem studies of human brains.

Inhibition of lysozyme fibrillation by human serum albumin nanoparticles: Possible mechanism.

Amyloid fibrillation is a prevalent phenomenon in different proteins and peptides, which results in a variety of disorders. Over the last decade, implementation of nanoparticles (NPs), with or without drugs, is considered as a promising approach to protect against the aggregation process of amyloid proteins. In this study, we investigated the effect of human serum albumin NPs (HSA NPs) on the fibrillation of Hen Egg White Lysozyme (HEWL).

Strong interactions with polyethylenimine-coated human serum albumin nanoparticles (PEI-HSA NPs) alter α-synuclein conformation and aggregation kinetics.

The interaction between nanoparticles (NPs) and the small intrinsically disordered protein α-synuclein (αSN), whose aggregation is central in the development of Parkinson's disease, is of great relevance in biomedical applications of NPs as drug carriers. Here we showed using a combination of different techniques that αSN interacts strongly with positively charged polyethylenimine-coated human serum albumin (PEI-HSA) NPs, leading to a significant alteration in the αSN secondary structure. In contrast, the weak interactions of αSN with HSA NPs allowed αSN to remain unfolded.