Abstract
Lysosomes are acidic cytoplasmic organelles that are present in nucleated mammalian cells and are involved in a variety of cellular processes including repair of the plasma membrane, defense against pathogens, cholesterol homeostasis, bone remodeling, metabolism, apoptosis and cell signaling. Defects in lysosomal enzyme activity have been associated with a variety of diseases including Parkinson's, Tay‐Sachs, Sandhoff, Krabbe and Gaucher's syndromes. New lysosomal staining probes useful for labeling lysosomes in a live‐cell format and capable of monitoring lysosomal metabolic activity have been developed. These new targeted substrates are based upon fluorescent probes that have a low pKa value for optimum fluorescence at the lower physiological pH values found in lysosomes, contain specific enzymatically‐cleavable functions for specific enzyme activities as well as targeting groups to direct their accumulation to the lysosomes using a live‐cell staining format. Application to the staining of cells derived from blood samples of patients with Metachromatic Leukodystrophy, Krabbe, Gaucher I, II and III, Tay‐Sach's and Sandhoff Diseases as well as healthy human fibroblast and leukocyte control cells are presented. In addition the ability to monitor the effect of secondary therapeutic agents on enzyme activity is presented. This work was supported by NIH Grant 5R44NS073225–04
Published Version
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