@article {737,
	title = {Lipid metabolic perturbation is an early-onset phenotype in adultmutants: amodel for lysosomal storage disorders. [Mass Spectrometry - Lipidomics]},
	journal = {Mol Biol Cell},
	volume = {28},
	year = {2017},
	month = {2017 Dec 15},
	pages = {3728-3740},
	abstract = {<p>Intracellular accumulation of lipids and swollen dysfunctional lysosomes are linked to several neurodegenerative diseases, including lysosomal storage disorders (LSD). Detailed characterization of lipid metabolic changes in relation to the onset and progression of neurodegeneration is currently missing. We systematically analyzed lipid perturbations inmutants, amodel of LSD-like neurodegeneration. Our results highlight an imbalance in brain ceramide and sphingosine in the early stages of neurodegeneration, preceding the accumulation of endomembranous structures, manifestation of altered behavior, and buildup of lipofuscin. Manipulating levels ofand altering these lipids inmutants allowed us to conclude that ceramide homeostasis is the driving force in disease progression and is integral tofunction in the adult nervous system. We identified 29 novel physical interaction partners of Spin and focused on the lipid carrier protein, Lipophorin (Lpp). A subset of Lpp and Spin colocalize in the brain and within organs specialized for lipid metabolism (fat bodies and oenocytes). Reduced Lpp protein was observed inmutant tissues. Finally, increased levels of lipid metabolites produced by oenocytes inmutants allude to a functional interaction between Spin and Lpp, underscoring the systemic nature of lipid perturbation in LSD.</p>
},
	keywords = {Animals, Carrier Proteins, Disease Models, Animal, Drosophila, Drosophila Proteins, Lipid Metabolism, Lipids, Lipoproteins, Lysosomal Storage Diseases, Lysosomes, Membrane Proteins, Mutation, Nervous System, Neurodegenerative Diseases, Phenotype},
	issn = {1939-4586},
	doi = {10.1091/mbc.E16-09-0674},
	author = {Hebbar, Sarita and Khandelwal, Avinash and Jayashree, R and Hindle, Samantha J and Chiang, Yin Ning and Yew, Joanne Y and Sweeney, Sean T and Schwudke, Dominik}
}
@article {712,
	title = {An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression.},
	journal = {Cell},
	volume = {151},
	year = {2012},
	month = {2012 Dec 21},
	pages = {1474-87},
	abstract = {<p>DNA Ligase IV is responsible for sealing of double-strand breaks (DSBs) during nonhomologous end-joining (NHEJ). Inhibiting Ligase IV could result in amassing of DSBs, thereby serving as a strategy toward treatment of cancer. Here, we identify a molecule, SCR7 that inhibits joining of DSBs in cell-free repair system. SCR7 blocks Ligase IV-mediated joining by interfering with its DNA binding but not that of T4 DNA Ligase or Ligase I. SCR7 inhibits NHEJ in a Ligase IV-dependent manner within cells,\&nbsp;and activates the intrinsic apoptotic pathway. More importantly, SCR7 impedes tumor progression in mouse models and when coadministered with DSB-inducing therapeutic modalities enhances their sensitivity significantly. This inhibitor to target NHEJ offers a strategy toward the treatment of cancer and improvement of existing regimens.</p>
},
	keywords = {Amino Acid Sequence, Animals, Cell Line, Tumor, Disease Models, Animal, DNA Breaks, Double-Stranded, DNA End-Joining Repair, DNA Ligase ATP, DNA Ligases, Drug Design, Drug Resistance, Neoplasm, Humans, Lymphocytes, Lymphoma, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Models, Molecular, Molecular Sequence Data, Neoplasms, Protein Structure, Tertiary, Pyrimidines, Radiation Tolerance, Rats, Schiff Bases, Sequence Alignment},
	issn = {1097-4172},
	doi = {10.1016/j.cell.2012.11.054},
	author = {Srivastava, Mrinal and Nambiar, Mridula and Sharma, Sheetal and Karki, Subhas S and Goldsmith, G and Hegde, Mahesh and Kumar, Sujeet and Pandey, Monica and Singh, Ram K and Ray, Pritha and Natarajan, Renuka and Kelkar, Madhura and De, Abhijit and Choudhary, Bibha and Raghavan, Sathees C}
}
