The neuronal ceroid lipofuscinoses (NCLs) are rare and fatal autosomal pediatric neurodegenerative disorders. The most prevalent subtype, CLN3, arises from a mutation in the CLN3 gene. Common phenotyp Show more
The neuronal ceroid lipofuscinoses (NCLs) are rare and fatal autosomal pediatric neurodegenerative disorders. The most prevalent subtype, CLN3, arises from a mutation in the CLN3 gene. Common phenotypic hallmarks include lipofuscin and subunit c of mitochondrial ATP synthase accumulation, mitochondrial dysfunction, and reduced Bcl-2 expression, however the underlying pathophysiology is not well understood. No effective treatment option exists. Herein, we report the synthesis and characterization of bicyclic analogues of the bioisosteric non-opioid analgesics Flupirtine and Retigabine, previously shown to exhibit neuroprotective effects. These analogues were strategically modified to prevent formation of toxic reactive diamine/diimine intermediates characteristic of the parent compounds. Novel 1 Show less
Metastatic progression in triple-negative breast cancer (TNBC) patients occurs primarily because of nuclear reprogramming that includes chromatin remodeling and epigenetic modifications. The existing Show more
Metastatic progression in triple-negative breast cancer (TNBC) patients occurs primarily because of nuclear reprogramming that includes chromatin remodeling and epigenetic modifications. The existing and most successful chemotherapies available for metastatic TNBC target nuclear proteins or damage DNA. The objectives here are to investigate an undescribed role for the molecular biology of nuclear angiopoietin-like protein 4 (ANGPTL4) and to characterize the effect of ectopic overexpression of ANGPTL4 in the metastatic biology of TNBC. Lentiviral-mediated transduction was used to overexpress ANGPTL4 in the TNBC cell line MD Anderson-metastatic breast cancer 231. The overexpression of ANGPTL4 was confirmed by western blot and ELISA. Subcellular fractionation, western blot, and immunofluorescence microscopy were used to characterize the intracellular localization of ANGPTL4. Mammosphere culture and the anchorage-independent growth assay analyzed the metastatic potential of the cell line. Xenograft assays assessed the effect of ANGPTL4 overexpression on TNBC metastases The ANGPTL4 overexpressing cell line formed larger mammospheres and anchorage-independent colonies The ANGPTL4 overexpressing cell line showed Show less