• The lysosomal pathway has, in the last few years, attracted interest as a novel mechanism involved in the pathogenesis of PD, following not only the identification of ATP13A2 mutations, but also the risk conferred by GBA mutations for the development of this disorder. (ucl.ac.uk)
  • These results show undisputable evidence that the lysosomal pathway plays a role in the pathogenesis of parkinsonian phenotypes and further suggest that KRS and NCL may share pathobiological features. (ucl.ac.uk)
  • Inhibition of the endo-lysosomal pathway with chloroquine or U18666A resulted in the formation of large Cyto-ID and Lyso-ID-positive compartments. (springer.com)
  • Using genetic, pharmacological, and metabolomic approaches, we demonstrate that caffeine reduces intrahepatic lipid content and stimulates β-oxidation in hepatic cells and liver by an autophagy-lysosomal pathway. (rti.org)
  • Here we report a novel pathway for lysosomal delivery of PGRN. (rupress.org)
  • We further showed that this PSAP pathway is independent of, but complementary to, the previously identified PGRN lysosomal trafficking mediated by sortilin. (rupress.org)
  • Notably, similar endosomal-lysosomal pathobiology emerges early in sporadic AD, where neuronal APP-βCTF is also elevated, underscoring its importance as a therapeutic target and underscoring the functional and pathogenic interrelationships between the endosomal-lysosomal pathway and genes causing AD. (jneurosci.org)
  • Our results further implicate the steroid signalling pathway and DAF-16 in dynamically regulating lysosomal pH in the intestine of wild-type worms in response to the reproductive cycle. (genetics.org)
  • Dysfunction of the autophagy-lysosomal pathway represents a key pathogenic event in GBA1 -associated neurodegeneration. (biologists.org)
  • To further investigate the mechanism of autophagy-lysosomal pathway dysfunction in neuronopathic GD, we examined mTORC1 kinase activity in GD iPSC neuronal progenitors and differentiated neurons. (biologists.org)
  • Our study uncovers a new mechanism contributing to autophagy-lysosomal pathway dysfunction in GD, and identifies the mTOR complex as a potential therapeutic target for treatment of GBA1 -associated neurodegeneration. (biologists.org)
  • Cathepsin B inhibitor reduced cell death and cytochrome c release in embelin-treated cells indicating lysosomal pathway as the upstream of mitochondrial death signaling. (biomedsearch.com)
  • Endocytic and autophagic substrates are degraded in ELs and ALs by lysosomal hydrolases. (nih.gov)
  • Direct measurements of lysosomal pH uncovered a significant elevation (0.6 units) as a basis for slowed LC3 turnover and the inactivation of cathepsin D and other lysosomal hydrolases known to be unstable or less active when lysosomal pH is persistently elevated. (jneurosci.org)
  • We then assessed the activity and maturation of lysosomal hydrolases from HCV-infected cells and determined that HCV did not decrease global lysosomal proteolytic activity. (ku.edu)
  • 2) TCA carcinogenesis is possibly mediated by lysosomal membrane destabilization, through cathepsin-D disruption, which could be reversed by AOLE administration. (hindawi.com)
  • 1. Limited lysosomal rupture induces activation of PLA2 (probably often mediated by the lysosomal enzyme, cathepsin B). (diva-portal.org)
  • Spi2A defects were ameliorated by cathepsin-B/L inhibition, and by genetic co-deletion of lysosomal cathepsin B. Pharmacological inhibition of cathepsin B/L enhanced EPO-induced red cell formation in normal mice. (rupress.org)
  • Overall, we define an unexpected EPO action mode via an EPOR-Spi2A serpin-cathepsin axis in maturing erythroblasts, with lysosomal cathepsins as novel therapeutic targets. (rupress.org)
  • In this study, we report on a novel EPO/EPOR-serpin-lysosomal cathepsin axis that can sharply modulate the survival of maturing erythroblasts as an unexpected target for cytoprotection. (rupress.org)
  • Quantitative real time PCR (qPCR) analysis was performed to study the expression of the following genes involved in lysosomal biogenesis and function: Lysosome associated membrane protein 1(LAMP-1), Cathepsin D (CTSD), Cathepsin A (CTSA), Cathepsin F (CTSF), hexosaminidase A, and ATPase, H+ transporting, lysosomal V0 subunit a1 (ATP6V0A1) encoding for a subunit of V-ATPase. (arvojournals.org)
  • Lysosomal destabilization and cathepsin B contributes for cytochrome c release and caspase activation in embelin-induced apoptosis. (biomedsearch.com)
  • Lysosomal role was further substantiated by enhanced cathepsin B activity noticed in embelin-treated cells. (biomedsearch.com)
  • p53-dependent lysosomal destabilization and cathepsin B activation contribute for increased sensitivity of p21-deficient cells to embelin with enhanced caspase 9 and caspase 3 activation. (biomedsearch.com)
  • Our results indicate rapid, possibly direct, transport of nascent class II-li complexes from the Golgi/trans-Golgi network to dense lysosomal compartments wherein cysteine protease(s), likely including cathepsin B, mediate complete removal of li. (jimmunol.org)
  • LSDs are pathologically typified by lysosomal inclusions composed of a heterogeneous mixture of various proteins and lipids that can be found throughout the body. (frontiersin.org)
  • As a result of lysosomal dysfunction and resultant disturbance of cellular homeostasis, LSDs have a broad spectrum of clinical manifestations including dysmorphism, visceromegaly, skeletal and joint abnormalities, hematologic findings and significant central and peripheral nervous system impairment. (neurologyadvisor.com)
  • Lower panel ) Lamp1 (Lysosome-associated membrane protein 1) surface staining allows one to monitor the insertion of lysosomal membrane proteins into the plasma membrane by using a monoclonal antibody against a luminal epitope of Lamp1 in non-permeabilized cells. (nih.gov)
  • Knockdown of the lysosomal membrane proteins LAMP1 and LAMP2 resulted in decreased cell viability, as did treatment of AML cells with known lysosome disrupters. (jci.org)
  • Malignant lysosomal distribution can be reverted by depletion of ErbB2 or cathepsins B and L. The possible regulatory role of MZF1 in the lysosome distribution has not been addressed before. (nature.com)
  • Lysosome positioning has been linked to lysosomal function. (rupress.org)
  • Schematic presentation of the regulation of metabolic signaling and lysosomal movement by the lysosome-associated Ragulator complex that consists of five LAMTOR subunits (LT1-5). (rupress.org)
  • The SENS rejuvenation research approach to lysosomal decline is to find ways to break down the specific molecular waste that the lysosome struggles with. (fightaging.org)
  • Although the function of the CHS/Beige protein is still poorly understood, its expression in beige-J cells restores normal lysosomal morphology ( 3 ). (pnas.org)
  • Immunofluorescence with mAbs against rat (LY1C6, provided by I. Mellman, Yale University, New Haven, CT), human (H4A3), or mouse (Protein Data Bank ID code 1D4B) lysosomal-associated membrane protein 1 (Lamp1) (Developmental Studies Hybridoma Bank, University of Iowa, Iowa City) was performed as described for attached cells ( 13 ). (pnas.org)
  • Lysosomal trafficking regulator is a vesicular transport protein associated with Chédiak-Higashi syndrome. (wikipedia.org)
  • In this paper we show that the susceptibility of protein antigens to lysosomal proteolysis plays an important role in determining immunogenicity in vivo. (rupress.org)
  • We found that prosaposin (PSAP) interacts with PGRN and facilitates its lysosomal targeting in both biosynthetic and endocytic pathways via the cation-independent mannose 6-phosphate receptor and low density lipoprotein receptor-related protein 1. (rupress.org)
  • In this article, we demonstrate that activator of G-protein signaling 3 (AGS3), an LPS-inducible protein in macrophages, affects both lysosomal biogenesis and activity. (jimmunol.org)
  • We will confirm the potential role as PD biomarker of CSF lysosomal enzyme activities, with special interest in GCase, and assess the impact of genetic factors (GBA1) on that activity. (michaeljfox.org)
  • Indeed, the specific inhibition of PLA2 by 4-bromophenacyl bromide (BPB ), diminishes both delayed lysosomal rupture and apoptosis. (diva-portal.org)
  • Furthermore, PLA2 activation by mellitin, or direct micro-injection of PLA2, causes lysosomal rupture and apoptosis. (diva-portal.org)
  • A critical step in the mediation of apoptotic signaling is the release of cathepsins to the cytosol, a process known as lysosomal membrane permeabilization (LMP). (diva-portal.org)
  • Myeloid Zinc Finger1 (MZF1) is an ErbB2-responsive transcription factor that promotes invasion of breast cancer cells via upregulation of lysosomal cathepsins B and L. Here we identify let-7 microRNA, a well-known tumor suppressor in breast cancer, as a direct negative regulator of MZF1. (nature.com)
  • These results demonstrate that lysosomal disruption preferentially targets AML cells and AML progenitor cells, providing a rationale for testing lysosomal disruption as a novel therapeutic strategy for AML. (jci.org)
  • AOLE introduced a promising therapeutic value in liver cancer, mostly through elevating lysosomal membrane integrity. (hindawi.com)
  • The objective of this study was to analyze if the transcriptional program regulating lysosomal biogenesis and function can be induced in the RPE following lysosomal disruption by treatment with ammonium chloride. (arvojournals.org)
  • Our studies suggest that perturbation of lysosomal function by pre-treatment with ammonium chloride followed by a recovery period results in a rapid induction of the transcriptional program that induces lysosomal biogenesis and function in ARPE-19 cells. (arvojournals.org)
  • The modest elevation of endogenous APP-βCTF needed to disrupt lysosomal function in DS is relevant to sporadic AD where APP-βCTF, but not APP, is also elevated. (jneurosci.org)
  • We then investigated whether enhancing lysosomal function can be beneficial. (fightaging.org)
  • Lysosomal channels and transporters mediate ion flux across perimeter membranes to regulate lysosomal ion homeostasis, membrane potential, catabolite export, membrane trafficking, and nutrient sensing. (nih.gov)
  • This delayed cell death seems to arise from activation of phospholipases, in particular phospholipase A2 (PLA2), which may dcstabilize lysosomal as well as mitochondrial membranes. (diva-portal.org)
  • Likewise, inhibitors of lysosomal functions also prevent gemcitabine-induced cell death. (springer.com)
  • Sphingosine-induced apoptosis was partly prevented by the inhibitors of lysosomal aspartic or cysteine proteases, pepstatin A or E64d. (diva-portal.org)
  • Taken together, these data demonstrate that lysosomal function is markedly impaired in atherosclerosis and suggest that induction of a lysosomal biogenesis program in macrophages has antiatherogenic effects. (fightaging.org)
  • Autophagic and endo-lysosomal degradative pathways are essential for cell homeostasis. (springer.com)
  • Although several probes have been recently developed to monitor autophagic or lysosomal compartments, their specificity has not been validated through co-localization studies with well-known markers. (springer.com)
  • These results constitute the first assessment of the selectivity of Cyto-ID and Lyso-ID as probes for the autophagic and lysosomal pathways, respectively. (springer.com)
  • Upper panel ) Lysosomal export and trafficking pathways. (nih.gov)
  • The lysosomal Ragulator complex regulates cell metabolism and growth by coordinating the activities of metabolic signaling pathways with nutrient availability. (rupress.org)
  • A switch in pathogenic mechanism in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in IFN-gamma-inducible lysosomal thiol reductase-free mice. (springer.com)
  • Delivery of nascent MHC class II-invariant chain complexes to lysosomal compartments and proteolysis of invariant chain by cysteine proteases precedes peptide binding in B-lymphoblastoid cells. (jimmunol.org)
  • Transcription factor EB (TFEB) is the only known transcription factor that is a master regulator of lysosomal biogenesis although its role in macrophages has not been studied. (fightaging.org)
  • Here, we explore the link between progeny production and somatic aging and identify the loss of lysosomal acidity, a critical regulator of the proteolytic output of these organelles, as a novel biomarker of aging in C. elegans . (genetics.org)
  • Using an induced pluripotent stem cell (iPSC) model of GD, we previously demonstrated that lysosomal alterations in GD neurons are linked to dysfunction of the transcription factor EB (TFEB). (biologists.org)
  • In intact cells, MSDH induces lysosomal rupture, oxidative stress and apoptosis. (diva-portal.org)
  • SAN RAFAEL, Calif., Feb. 9, 2015 (GLOBE NEWSWIRE) -- BioMarin Pharmaceutical Inc. (Nasdaq:BMRN) announced today that the company would make two data presenations in addition to presenting eight posters at the Lysosomal Disease Network's 11th Annual WORLD Symposium™ from February 9-13 in Orlando, Florida. (cnbc.com)