Monitoring autophagy in Alzheimer's disease and related neurodegenerative diseases.
AuthorsYang DS, Lee JH, Nixon RA,
JournalMethods Enzymol
PubMed ID19216904
'This chapter describes detailed methods to monitor autophagy in neurodegenerative disorders, especially in Alzheimer''s disease. Strategies to assess the competence of autophagy-related mechanisms in disease states ideally incorporate analyses of human disease and control tissues, which may include brain, fibroblasts, or other peripheral cells, in addition to animal and cell ... More
Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer's disease.
AuthorsBoland B, Kumar A, Lee S, Platt FM, Wegiel J, Yu WH, Nixon RA,
JournalJ Neurosci
PubMed ID18596167
'Macroautophagy, a major pathway for organelle and protein turnover, has been implicated in the neurodegeneration of Alzheimer''s disease (AD). The basis for the profuse accumulation of autophagic vacuoles (AVs) in affected neurons of the AD brain, however, is unknown. In this study, we show that constitutive macroautophagy in primary cortical ... More
Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations.
AuthorsLee JH, Yu WH, Kumar A, Lee S, Mohan PS, Peterhoff CM, Wolfe DM, Martinez-Vicente M, Massey AC, Sovak G, Uchiyama Y, Westaway D, Cuervo AM, Nixon RA,
JournalCell
PubMed ID20541250
Macroautophagy is a lysosomal degradative pathway essential for neuron survival. Here, we show that macroautophagy requires the Alzheimer's disease (AD)-related protein presenilin-1 (PS1). In PS1 null blastocysts, neurons from mice hypomorphic for PS1 or conditionally depleted of PS1, substrate proteolysis and autophagosome clearance during macroautophagy are prevented as a result ... More
Targeted delivery of antigen processing inhibitors to antigen presenting cells via mannose receptors.
AuthorsRaiber EA, Tulone C, Zhang Y, Martinez-Pomares L, Steed E, Sponaas AM, Langhorne J, Noursadeghi M, Chain BM, Tabor AB,
JournalACS Chem Biol
PubMed ID20349916
Improved chemical inhibitors are required to dissect the role of specific antigen processing enzymes and to complement genetic models. In this study we explore the in vitro and in vivo properties of a novel class of targeted inhibitor of aspartic proteinases, in which pepstatin is coupled to mannosylated albumin (MPC6), ... More
NAADP, cADPR and IP3 all release Ca2+ from the endoplasmic reticulum and an acidic store in the secretory granule area.
AuthorsGerasimenko JV, Sherwood M, Tepikin AV, Petersen OH, Gerasimenko OV
JournalJ Cell Sci
PubMed ID16410548
Inositol trisphosphate and cyclic ADP-ribose release Ca2+ from the endoplasmic reticulum via inositol trisphosphate and ryanodine receptors, respectively. By contrast, nicotinic acid adenine dinucleotide phosphate may activate a novel Ca2+ channel in an acid compartment. We show, in two-photon permeabilized pancreatic acinar cells, that the three messengers tested could each ... More
Probing the cathepsin D using a BODIPY FL-pepstatin A: applications in fluorescence polarization and microscopy.
AuthorsChen CS, Chen WN, Zhou M, Arttamangkul S, Haugland RP
JournalJ Biochem Biophys Methods
PubMed ID10737220
Redistribution of cathepsin D, a major lysosomal aspartic endopeptidase, has been related to various pathological progressions during tumor formation and oxidation stress. We have synthesized a fluorescent probe for cathepsin D, where the pepstatin A was covalently conjugated with the BODIPY (Boron dipyrromethene difluoride) fluorophore. In vitro, BODIPY FL-pepstatin A ... More
Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation.
Authors
JournalJ Clin Invest
PubMed ID25365221
Involvement of CASP9 (caspase 9) in IGF2R/CI-MPR endosomal transport.
Authors
JournalAutophagy
PubMed ID32397873
Impaired mitophagy links mitochondrial disease to epithelial stress in methylmalonyl-CoA mutase deficiency.
Authors
JournalNat Commun
PubMed ID32080200
C9orf72 and smcr8 mutant mice reveal MTORC1 activation due to impaired lysosomal degradation and exocytosis.
Authors
JournalAutophagy
PubMed ID31847700
ATM loss disrupts the autophagy-lysosomal pathway.
Authors
JournalAutophagy
PubMed ID32757690
Compromised phagosome maturation underlies RPE pathology in cell culture and whole animal models of Smith-Lemli-Opitz Syndrome.
Authors
JournalAutophagy
PubMed ID29979914
A growth-factor-activated lysosomal K+ channel regulates Parkinson's pathology.
Authors
JournalNature
PubMed ID33505021
Impaired autophagy bridges lysosomal storage disease and epithelial dysfunction in the kidney.
Authors
JournalNat Commun
PubMed ID29323117
SNAPIN is critical for lysosomal acidification and autophagosome maturation in macrophages.
Authors
JournalAutophagy
PubMed ID27929705
A family of PIKFYVE inhibitors with therapeutic potential against autophagy-dependent cancer cells disrupt multiple events in lysosome homeostasis.