Disease relevance of Ppt1

• Palmitoyl protein thioesterase (PPT) is the defective enzyme in infantile neuronal ceroid lipofuscinosis (INCL), which is a recessively inherited, progressive neurodegenerative disorder [1].
• Therefore, the PPT sequence may, in a gene therapy setting, be beneficial to prostate cancer patients that have been treated with androgen withdrawal [2].
• Therefore, we believe that an adenovirus with therapeutic gene expression controlled by an insulator-shielded PPT sequence is a promising candidate for gene therapy of prostate cancer [2].
• Female B57BL/J6 ER-beta(-/-) transgenic mice [knockout (KO)] and corresponding ovariectomized wild-type (WT) mice were subjected to laparotomy and hemorrhagic shock (35.0+/-5.0 mmHg for 90 min) and treated with E2 (50 microg/25 g) or ER-alpha agonist propyl pyrazole triol (PPT; 50 microg/25 g) following trauma-hemorrhage [3].

High impact information on Ppt1

• Palmitoyl-protein thioesterase-1 deficiency mediates the activation of the unfolded protein response and neuronal apoptosis in INCL [4].
• Palmitoyl-protein thioesterase-1 deficiency leads to the activation of caspase-9 and contributes to rapid neurodegeneration in INCL [5].
• A deficiency of palmitoyl protein thioesterase (PPT) leads to the neurodegenerative disease infantile neuronal ceroid lipofuscinosis (INCL), which is characterized by an almost complete loss of cortical neurons [6].
• Transient expression of mouse PPT in COS-1 cells yielded a 38/36-kD differentially glycosylated polypeptide that was also secreted into culture media [1].
• Fluorescence in situ hybridization to metaphase chromosomes localized the mouse PPT gene to the chromosome 4 conserved syntenic region with human chromosome 1p32 where the human PPT is located [1].

Biological context of Ppt1

• Pre-sertoli specific gene expression profiling reveals differential expression of Ppt1 and Brd3 genes within the mouse genital ridge at the time of sex determination [7].
• We have investigated the onset and progression of pathological changes in Ppt1 deficient mice (Ppt1-/-) and the development of their seizure phenotype [8].
• The mouse PPT gene spans >21 kb of genomic DNA and contains nine exons with a coding sequence of 918 bp [1].
• The mouse PPT cDNA is conserved highly with the human and rat PPT both at the nucleotide and amino acid sequence level [1].
• A recombinant adenovirus vector with the PPT sequence, shielded from interfering adenoviral sequences by the mouse H19 insulator, yields high and prostate-specific transgene expression both in cell cultures and when prostate cancer, PC-346C, tumors were grown orthotopically in nude mice [2].

Anatomical context of Ppt1

• These findings provide novel evidence for successive neuron loss within the thalamus and cortex in Ppt1-/- mice, revealing the thalamus as an important early focus of INCL pathogenesis [8].
• Immunofluorescence analysis of transiently transfected HeLa cells indicated lysosomal localization of mouse PPT [1].
• Furthermore, we show that saposins A and D are more abundant and relocalized in PPT-deficient fibroblasts and mouse primary neurons [9].
• Although the suppression in the productive capacity of these cytokines following trauma-hemorrhage by macrophages and splenocyte was also prevented in E2- and PPT-treated WT mice, the release of cytokines by macrophages and splenocytes in E2- and PPT-treated KO mice was not restored to the levels observed in sham animals [3].
• We have investigated the relaxant actions of PPT and DPN in rat and mouse aorta and mesenteric artery [10].

Associations of Ppt1 with chemical compounds

• Inactivating mutations in the Dolpp1p domain do not rescue the lethality, whereas mutations in the Ppt1p domain result in cells that are viable but abnormally sensitive to sodium orthovanadate and elevated extracellular pH [11].

Other interactions of Ppt1

• The expression pattern of two genes, Ppt1 and Brd3, were examined in further detail [7].

References