Disease relevance of APP

• Neither hippocampal nor cortical levels of the APP holoprotein (APP(h)), nor body weight, were affected by DEXNOR [1].
• We have been characterizing porcine plasma lectins that bind in a carbohydrate-dependent manner to surfaces of important bacterial pig pathogens including Actinobacillus suis (AS), A. pleuropneumoniae (APP), and Haemophilus parasuis (HP) [2].
• Neuronal perikaryal APP expression was also widely distributed, possibly as an acute phase response to this neurotoxin [3].

Psychiatry related information on APP

• Soluble and membrane-bound isoforms of beta-amyloid protein precursor (APP) of Alzheimer's disease were extracted and purified from porcine brains [4].

High impact information on APP

• Disrupted anterograde axonal transport and resulting beta-amyloid precursor protein (APP) accumulation are byproducts of traumatic axonal injury (TAI) in the brain [5].
• Increased APP expression after injury was abolished in the thalamus and reduced in the medial longitudinal fasciculus by PEG treatment [5].
• APP accumulation indicates axonal degeneration as a result of axotomy, a detriment that can lead to cell death [5].
• We have recently shown that in utero treatment of guinea pigs with the DNA methylating substance methylazoxymethanol acetate (MAM) results in neocortical microencephalopathy, increased protein kinase C (PKC) activity and altered processing of the amyloid precursor protein (APP) in neocortex of offspring [6].
• Here we show that PKCalpha and PKCbeta1 are the key regulators of alpha-secretory APP processing in guinea pig neocortex under these experimental conditions in vivo [6].

Biological context of APP

• This upregulation of APP alpha-secretion was limited to brain areas that displayed elevated PKC activity [7].
• We have previously reported the construction of genetically-defined stable riboflavin auxotrophs by replacement of a portion of the APP riboflavin biosynthetic operon (ribGBAH) with an antibiotic cassette encoding resistance to kanamycin, and have demonstrated that such riboflavin auxotrophs are avirulent [8].
• CONCLUSIONS: The failure of these vaccines to provide protection against serovar 15 may be due to novel virulence factors possessed by serovar 15, significant differences between the ApxIII toxin of serovar 15 and those present in the Porcilis APP vaccine or failure by both vaccines to induce antibodies to the serovar 15 specific polysaccharide [9].

Anatomical context of APP

• APP injected into a subphase induced a substantial increase in the surface pressure of monolayers prepared from PC (L-alpha-phosphatidylcholine), Chol, SPM (sphingomyelin) and PS (L-alpha-phosphatidylserine), the major lipids present in the plasma membranes of brain cells [10].
• These observations may be related to the partitioning of APP into membrane microdomains [11].
• Stimulation of serotonin receptor subtypes 5-HT(2A) or 5-HT(2C) in stably transfected 3T3 cells by dexnorfenfluramine (DEXNOR) or serotonin increases secretion of the APP metabolite APP(s) [1].
• Immunoblots of outer membranes (OM) prepared from APP 1A or 1B reference strains and field isolates indicated that antigenic differences between subtypes 1A and 1B were located within the high molecular weight (MW) region of the gels (40-100 kDa) [12].
• We used both enzyme-linked immunosorbent assay (ELISA) and LPECL methods to measure A beta and APPs alpha levels in conditioned medium of beta-amyloid precursor protein (APP)-transfected CHO cells treated with known modulators of APP processing, and in CSF and plasma of guinea pigs [13].

Associations of APP with chemical compounds

• In the same cortical/hippocampal preparations of methylazoxymethanol-treated animals, there was increased alpha-secretion of APP by 35% and 30% as measured by Western blot analysis using the antibody 6E10, whilst total APP secretion as well as APP mRNA expression remained unaltered [7].
• Amyloid precursor protein (APP) immunocytochemistry was used to study axonal and neuronal changes in guinea pig brains exposed to tunicamycin [3].
• DESIGN: The Porcilis APP vaccine and an experimental streptomycin-dependent strain of A pleuropneumoniae were evaluated in a standardised pen trial [14].

Other interactions of APP

• In the serovar 15 challenged pigs, the only significant difference detected was that the Porcilis APP vaccinated pigs had a better postchallenge ADG than the controls [14].
• There was evidence that the Porcilis APP vaccine did provide some protection against the serovar 15 challenge because the ADG, after challenge of pigs given this vaccine, was greater than the control pigs [14].

Analytical, diagnostic and therapeutic context of APP

• However, constitutive overactivation of neocortical PKC did not affect the generation of beta-amyloid peptides 1-40 or 1-42 as measured by ELISA, suggesting that only the alpha-secretase pathway of APP processing is affected by chronic PKC overactivation in vivo [7].
• CD and infrared spectroscopies were used to determine the overall secondary-structure content of APP [4].
• SDS-PAGE gels with LPS purified from APP 1A, 1B, 9 and 11 showed that 1A, 9 and 11 LPS O-antigens had an identical smooth ladder pattern, while 1B LPS was distinctly different [12].
• The results of the new PCR were compared with a PCR based on the detection of the omlA gene coding for an outer membrane protein, with a commercially available PCR (Adiavet APP, Adiagène, Saint-Brieuc, France), and with conventional culturing [15].
• RESULTS: With the serovar 1 challenge, the Porcilis APP vaccine and the live vaccine, compared with the control group, gave significant protection in terms of clinical signs, lung lesions, re-isolation scores and average daily gain (ADG) postchallenge [14].

References