The lysosome, initially discovered by Christian de Duve in 1955, is an intracellular organelle responsible of the ordered degradation of proteins, glycoproteins, proteoglycans, lipids, and other macromolecules originated from autophagy, endocytosis and phagocytosis. It is characterize by a limiting external membrane containing intraluminal vesicles. These organelles are estimated to contain 50-...

The aim of the project “Small molecule regulators of vesicular trafficking to enhance lysosomal exocytosis in cystinosis” is to use strategies directed at upregulating the exocytic pathway in cystinotic cells, in order to improve vesicular transport, force cystine release and restore normal cell function. Our hypothesis, in fact, states that cells that have accumulated cystine share the intrace...

BACKGROUND Lysosomal storage diseases (LSD) are inherited disorders caused by deficiency of lysosomal enzymes in which early diagnosis is essential to provide timely treatment. This study reports interval values for the activity of lysosomal enzymes that are deficient in Mucopolysaccharidosis type I, Fabry, Gaucher and Pompe disease, using dried blood spots on filter paper (DBS) samples in a Br...

Robust activation of the neuronal lysosomal system and cellular pathways converging on the lysosome, such as the endocytic and autophagic pathways, are prominent neuropathological features of Alzheimer's disease. Disturbances of the neuronal endocytic pathway, which are one of the earliest known intracellular changes occurring in Alzheimer's disease and Down syndrome, provide insight into how b...

A defective efflux of free sialic acid from the lysosomal compartment has been found in the clinically heterogeneous group of sialic acid storage disorders. Using radiolabeled sialic acid (NeuAc) as a substrate, we have recently detected and characterized a proton-driven carrier for sialic acid in the lysosomal membrane from rat liver. This carrier also recognizes and transports other acidic mo...

BACKGROUND Interest in lysosomal storage disorders, a collection of more than 40 inherited metabolic disorders, has increased because of new therapy options such as enzyme replacement, stem cell transplantation, and substrate reduction therapy. We developed a high-throughput protocol that simplifies analytical challenges such as complex sample preparation and potential interference from excess ...

Chloroacetaldehyde (CAA) is a chlorination by-product in finished drinking water and a toxic metabolite of a wide variety of industrial chemicals (e.g. vinyl chloride) and chemotherapeutic agents (e.g. cyclophosphamide and ifosfamide). In this research, the cytotoxic mechanisms of CAA in freshly isolated rat hepatocytes were investigated.CAA cytotoxicity was associated with reactive oxygen spec...

For a long time lysosomes were considered terminal organelles involved in the degradation of different substrates. However, this view is rapidly changing by evidence demonstrating that these organelles and their content display specialized functions in addition to the degradation of substances. Many lysosomal proteins have been implicated in specialized cellular functions and disorders such as ...

BMP [bis(monoacylglycero)phosphate] is an acidic phospholipid and a structural isomer of PG (phosphatidylglycerol), consisting of lysophosphatidylglycerol with an additional fatty acid esterified to the glycerol head group. It is thought to be synthesized from PG in the endosomal/lysosomal compartment and is found primarily in multivesicular bodies within the same compartment. In the present st...

Classical approaches to the study of pathological tissue have relied mainly on morphological techniques. In an attempt to quantitate the abnormalities and to investigate the pathogenesis of tissue disorders at a subcellular level we have combined analytical subcellular fractionation by sucrose density gradient centrifugation with microanalysis of tissue enzymic activities. The methodological pr...