Disease relevance of TPPP

• In contrast, TPPP/p25 is not associated with abnormally phosphorylated tau in various inclusions of Pick's disease (PiD), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) [1].
• Immunohistochemistry and confocal microscopy demonstrates that TPPP/p25 is enriched in filamentous alpha-synuclein bearing Lewy bodies of Parkinson's (PD) and diffuse Lewy body disease (DLBD), as well as glial inclusions of multiple system atrophy (MSA) [1].
• The brain-specific protein TPPP/p25 in pathological protein deposits of neurodegenerative diseases [2].
• SK-N-MC neuroblastoma cells were transfected with pEGFP-TPPP/p25 construct and a stable clone denoted K4 was selected and used to establish the effect of this unstructured protein on the energy state/metabolism of the cells [3].
• Infected animals were found to mount a specific, strong, long-lasting CD8+ cytolytic T cell response against a predominant epitope contained within the p24 fragment of the HIV Gag protein [4].

Psychiatry related information on TPPP

• However, electron microscopy confirms clusters of TPPP/p25 immunoreactivity along filaments of unstructured but not compact neurofibrillary tangles in Alzheimer's disease (AD) [1].

High impact information on TPPP

• These studies suggest that platelet activation mediated by the surface protein p24/CD9 is mainly through the stimulation of a phospholipase C, the activation of which is responsible for the generation of second messengers inositol trisphosphate and DAG [5].
• We show that at low expression levels EGFP-TPPP/p25 specifically colocalizes with the microtubule network of HeLa and NRK cells [6].
• Time-lapse and immunofluorescence experiments revealed that high levels of EGFP-TPPP/p25 inhibited cell division and promoted cell death [6].
• We propose that a potential function of TPPP/p25 is the stabilization of physiological microtubular ultrastructures, however, its upregulation may directly or indirectly initiate the formation of aberrant protein aggregates such as pathological inclusions [6].
• Having localized its expression to neuronal tissue by Western blot analyses, the distribution of p25alpha/TPPP to developing oligodendrocytes was confirmed using a specific antibody [7].

Biological context of TPPP

• Dynamic targeting of microtubules by TPPP/p25 affects cell survival [6].
• A novel human gene whose product shares significant homology with the bovine brain-specific protein p25 on chromosome 5p15.3 [8].
• TPPP/p25, the first representative of a new protein family, identified as a brain-specific unfolded protein induces aberrant microtubule assemblies in vitro, suppresses mitosis in Drosophila embryo and is accumulated in inclusion bodies of human pathological brain tissues [3].
• A heat resistant glycogen synthase kinase 3 (GSK 3) binding protein, p24, that inhibits its kinase activity at a low magnesium concentration (in a way similar to that of lithium) was found in microtubules from adult rat brains [9].
• Here we present molecular-cytogenetic and cytogenetic investigations on a follicular thyroid adenoma with a t(2;20;3)(p21;q11.2; p25) [10].

Anatomical context of TPPP

• Interaction of TPPP/p25 protein with glyceraldehyde-3-phosphate dehydrogenase and their co-localization in Lewy bodies [11].
• In the mature brain, p25alpha/TPPP distributes to oligodendrocytes and choroid plexus epithelium [7].
• In transfected HeLa cells at low expression level of EGFP-TPPP/p25, while the green fusion protein aligned at the microtubular network, GAPDH distributed uniformly in the cytosol [11].
• Our data by analyzing the mitochondrial membrane polarization by fluorescence microscopy revealed that the high-energy phosphate production in K4 clone is not damaged by the TPPP/p25 expression [3].

Associations of TPPP with chemical compounds

• Our modelling using these data and rate equations of the individual enzymes suggests that the TPPP/p25 expression stimulates glucose metabolism [3].
• Generation, characterization and cross-reactivities of monoclonal antibodies against the p24 core protein and the gp130 envelope glycoprotein of HIV-2ben [12].

Regulatory relationships of TPPP

• The combination of our in vitro and in vivo data suggests that ERK2 can regulate TPPP activity via the phosphorylation of Thr(14) and/or Ser(18) in its unfolded N-terminal tail [13].

Co-localisations of TPPP

• However, at high expression level, GAPDH co-localized with TPPP/p25 in the aggresome-like aggregate [11].

Other interactions of TPPP

• We tested three different epitope unmasking methods, we applied laser confocal microscopy to evaluate double immunolabelling, and we compared the amount of structures exhibiting TPPP/p25 and alpha-synuclein immunoreactivity [2].
• Oligodendrocyte progenitor cells and pre-myelinating oligodendrocytes identified by the expression of NG2 proteoglycan and CD9, respectively, both failed to contain p25alpha/TPPP [7].
• In the pre-natal and post-natal brain, p25alpha/TPPP was localized to the perinuclear cytoplasm of myelinating oligodendrocytes from embryonic (E) day E20 as verified from cellular co-localization with 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) [7].

Analytical, diagnostic and therapeutic context of TPPP

• There is a correlation between TPPP/p25 and alpha-synuclein immunoreactivity in Western blot [1].
• The previous and the present studies obtained with immunohistochemistry with pathological human brain tissues rendered it possible to classify among pathological inclusions on the basis of immunolabelling of TPPP/p25, and suggest this protein to be a potential linkage between Parkinson's and Alzheimer's diseases [3].
• Evaluation of a new fourth generation enzyme-linked immunosorbent assay, the LG HIV Ag-Ab Plus, with a combined HIV p24 antigen and anti-HIV-1/2/O screening test [14].

References