STUDIES ON PALMITOYL-PROTEIN THIOESTERASE 1 Implications for synaptic functions

PDF created with FinePrint pdfFactory Pro trial version enzyme implicated in neurodegeneration, is localized in neurons and is developmentally regulated in rat brain. The expression of palmitoyl-protein thioesterase is developmentally regulated in neural tissues but not in nonneural tissues. changes in the expression of neuronal ceroid lipofuscinoses-linked proteins. Mol Genet Status epilepticus induces changes in the expression and localization of endogenous palmitoyl protein thioesterase 1. Accepted to Neurobiology of Disease. 7 ABBREVIATIONS aa amino acid AMPA DL-a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid BSA bovine serum albumine Ca 2+ calcium CLN1 infantile neuronal ceroid-lipofuscinosis CLN2 late-infantile neuronal ceroid-lipofuscinosis CLN2p CLN2 protein = tripeptidyl peptidase 1 pepstatin-insensitive proteinase CLN3 juvenile neuronal ceroid-lipofuscinosis CNS central nervous system CONCL congenital ovine neuronal ceroid-lipofuscinosis Da dalton DAB diaminobenzidine tetrahydrochloride DNA deoxyribonucleic acid E11 embryonic day 11 EM electron microscopy ER endoplasmic reticulum FITC fluorescein isothiocyanate GAP-43 growth-associated protein 43 kDa GRODs granular osmiophilic deposits Hepes N-(2-Hydroxyethyl)piperazine-N'(2-ethanesulfonic acid) INCL classic infantile neuronal ceroid-lipofuscinosis KA kainic acid kDa kilodalton LINCL classic late-infantile neuronal ceroid lipofuscinosis LTD long-term depression LTP long-term potentiation Man 6-P mannose 6-phosphate MRI magnetic resonance imaging mRNA messenger ribonucleic acid NCL neuronal ceroid-lipofuscinosis NMDA N-methyl-D-aspartate NMDAR N-methyl-D-aspartate receptor Palmitoyl-CoA palmitoyl-Coenzyme A P15 postnatal day 15 PBS phosphate-buffered saline PET positron emission tomography PPT1 palmitoyl-protein thioesterase 1 PSD postsynaptic density PSD-95 postsynaptic density protein, 95 kDa RNA ribonucleic acid RT-PCR reverse transcription polymerase chain reaction SAP90 synapse-associated protein, 90 kDa saposins sphingolipid activator proteins SDS-PAGE sodium dodecyl sulfate polyacrylamide gel electrophoresis SNAP-25 synaptosomal-associated protein 25 kDa TBS tris buffered saline TPP-I tripeptidyl peptidase I TRITC tetramethylrhodamine isothiocyanite PDF created with FinePrint pdfFactory Pro trial version 8 INTRODUCTION A storage disease, a lysosomal disease, a lysosomal storage disease, a neurodegenerative disease, and a progressive encephalopatia are definitions applying for infantile neuronal ceroid-lipofuscinosis, INCL (CLN1). It is one of the most severe of the inherited diseases affecting children worldwide. Clinically, genetically, and pathologically INCL has been well characterized. However, due to difficulties in studying the developing human brain, investigations of the pathogenesis and mechanisms causing INCL have progressed slowly. Normal development of an INCL-child during the first year of life is followed by dramatic and rapid deterioration of the central nervous system (CNS). Since the onset of INCL appears while synaptogenesis is ongoing, the mechanisms halting the normal infantile progress most possibly are involved in forming or maintaining neuronal connections. The defective protein causing this devastating disease is a lysosomal …