Many hereditary diseases are characterized by region-specific toxicity, despite the fact that disease-linked proteins are generally ubiquitously expressed. The underlying basis of the region-specific vulnerability remains enigmatic. Here, we evaluate the fundamental features of mitochondrial and glucose metabolism in synaptosomes from four brain regions in basal and stressed states.
View Article and Find Full Text PDFMany trinucleotide repeat disorders exhibit region-specific toxicity within tissues, the basis of which cannot be explained by traditional methods. For example, in Huntington's Disease (HD), the toxic disease-causing protein is ubiquitously expressed. However, only the medium spiny neurons in the striatum are initially targeted for death.
View Article and Find Full Text PDFIn a variety of neurological diseases, pathological progression is cell type and region specific. Previous reports suggest that mass spectrometry imaging has the potential to differentiate between brain regions enriched in specific cell types. Here, we utilized a matrix-free surface mass spectrometry approach, nanostructure initiator mass spectrometry (NIMS), to show that spatial distributions of multiple lipids can be used as a 'fingerprint' to discriminate between neuronal- and glial- enriched brain regions.
View Article and Find Full Text PDFParticulate delivery systems enhance antibody responses to subunit antigens. However, covalent attachment of protein antigens can disrupt protein structure and mask critical epitopes, altering the antibody response to the antigen. In this report, we evaluate noncovalent metal chelation via nitrilotriacetic acid (NTA) as a nondestructive method to attach peptide and protein antigens to liposomes.
View Article and Find Full Text PDFMetal chelation-ligand interactions, such as occur between nitrilotriacetic acid (NTA)-nickel and multihistidines, enable the noncovalent attachment of histidine-modified proteins to liposomes and other particles. We compared three lipids: a mono-NTA lipid (ca. 10 microM affinity) and two tris-NTA lipid derivatives (ca.
View Article and Find Full Text PDFMatrix attachment therapy (MAT) is an enzyme prodrug strategy that targets hyaluronan in the tumor extracellular matrix to deliver a prodrug converting enzyme near the tumor cells. A recombinant fusion protein containing the hyaluronan binding domain of TSG-6 (Link) and yeast cytosine deaminase (CD) with an N-terminal His(x6) tag was constructed to test MAT on the C26 colon adenocarcinoma in Balb/c mice that were given 5-fluorocytosine (5-FC) in the drinking water. LinkCD was expressed in Escherichia coli and purified by metal-chelation affinity chromatography.
View Article and Find Full Text PDFThe complex system involved in the synthesis, degradation and binding of the high molecular weight glycosaminoglycan hyaluronic acid (hyaluronan or HA) provides a variety of structures that can be exploited for targeted cancer therapy. In many cancers of epithelial origin there is an upregulation of CD44, a receptor that binds HA. In other cancers, HA in the tumor matrix is overexpressed.
View Article and Find Full Text PDF