Extracellular vesicles (EVs) are a heterogeneous population of stable lipid membrane particles that play critical role in the regulation numerous physiological and pathological processes. EV cargo, which includes lipids, proteins, RNAs including miRNAs, is affected by metabolic status parental cell. Concordantly, abnormalities autophagic-endolysosomal pathway, as seen lysosomal storage disorder...

Prions are proteinaceous infectious particles which cause fatal neurodegenerative disorders in humans and animals. They consist of a mostly β-sheeted aggregated isoform (PrP(Sc)) of the cellular prion protein (PrP(c)). Prions replicate autocatalytically in neurons and other cell types by inducing conformational conversion of PrP(c) into PrP(Sc). Within neurons, PrP(Sc) accumulates at the plasma...

Intraneuronal, largely proteinaceous aggregates accumulate in all major neurodegenerative disorders. Lysosomal degradation of proteinaceous and other material declines early in such diseases. This suggests that intraneuronal aggregates consist of material which is normally broken down in the lysosome and thus accumulates when lysosomal degradation fails. This is plausible even though those aggr...

The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in lysosomal acidification has been difficult to determine. We demonstrate here that CFTR contributes more to the reacidification of lysosomes from an elevated pH than to baseline pH maintenance. Lysosomal alkalinization is increasingly recognized as a factor in diseases of accumulation, and we previously showed that cAM...

The level of serum beta-glucuronidase increases in various pathological conditions, including liver disorders. The aim of this investigation was to study the changes in liver lysosomal membrane stability during experimentally induced hepatic fibrosis that may result in the elevation of serum beta-glucuronidase. Liver injury was induced by intraperitoneal injections of N-nitrosodimethylamine (ND...

The autophagy-lysosomal pathway plays an important role in the clearance of long-lived proteins and dysfunctional organelles. Lysosomal dysfunction has been implicated in several neurodegenerative disorders including Parkinson's disease and related synucleinopathies that are characterized by accumulations of α-synuclein in Lewy bodies. Recent identification of mutations in genes linked to lysos...