Biomedical subjects

F Van Leuven

Publications and source records attributed to F Van Leuven.

At least 19 recordsLinked to original sources

PubMed2003

Alpha-2 macroglobulin controls trophoblast positioning in mouse implantation sites.

In humans, functional deficiency of alpha-2M is not known, implying alpha 2M is essential for gestational success. Mice, deficient in two members of the alpha-2 Macroglobulin (alpha 2M) family, i.e. alpha-2 macroglobulin (MAM) and murinoglobulin-1 (MUG-1) are viable, fertile and phenotypically normal, unless stressed (Am J Pathol, 155 (1999), 983). Here, we analysed implantation sites in MAM(-/-)/MUG-1(-/-)mice during pregnancy, a strong physiological stressor. Despite some post-implantation fetal loss, mean litter size was comparable to congenic C57Bl/6J (B6) mice, but MAM(-/-)/MUG-1(-/-)pups were significantly lighter and the sex ratio was skewed towards males. Implantation sites appeared histologically normal up to gestational day (gd) 8. By gd 10, extensive over-development of trophoblasts was evident, accompanied by relative deficits in decidua, in the mural mesometrial lymphoid aggregates of pregnancy and in uterine Natural Killer cells. At gd 10-12, decidual spiral arteries were dilated but abnormally cuffed by trophoblasts that extended anomalously, for midgestation, to the myometrial circular smooth muscle. Ultrastructurally, trophoblasts in the mesometrial decidua made intimate contact with endothelial cells that were shedding membrane fragments. These findings demonstrate that alpha 2M, and thereby proteinases and/or cytokines whose bio-availability is regulated by alpha 2M, exert significant decidual regulation on trophoblast invasion.

Animals↗

PubMed2002

Coexpression of GSK-3beta corrects phenotypic aberrations of dorsal root ganglion cells, cultured from adult transgenic mice overexpressing human protein tau.

Coexpression of constitutively active GSK-3beta[S9A] rescued the axonal pathology induced by overexpression of human tau in transgenic mice (Spittaels et al., (2000) J. Biol. Chem. 275, 41340-41349). We isolated dorsal root ganglion (DRG) neuronal cultures from adult tau4R- and tau4R x GSK-3beta-transgenic mice to define the mechanisms at the cellular and subcellular level. DRG from tau4R-transgenics showed a reduced sprouting capacity while density and stability of microtubules in the axonal processes were significantly increased. Video-enhanced contrast microscopy demonstrated a dramatic inhibition of fast axonal transport. Coexpression of GSK-3beta increased tau phosphorylation and reversed the effects on microtubule stability and saltatory motion. In DRG from GSK-3beta single transgenics, increased tau phosphorylation was evident without any major effects on microtubule stability or axonal transport. These observations support the hypothesis that excess tau competed with motor-proteins for binding to microtubules and/or that a rigid microtubular system inhibits axonal transport.

Acetylation↗

PubMed2002

Neonatal neuronal overexpression of glycogen synthase kinase-3 beta reduces brain size in transgenic mice.

Glycogen synthase kinase-3beta (GSK-3beta) is important in neurogenesis. Here we demonstrate that the kinase influenced post-natal maturation and differentiation of neurons in vivo in transgenic mice that overexpress a constitutively active GSK-3beta[S9A]. Magnetic resonance imaging revealed a reduced volume of the entire brain, concordant with a nearly 20% reduction in wet brain weight. The reduced volume was most prominent for the cerebral cortex, without however, disturbing the normal cortical layering. The resulting compacted architecture was further demonstrated by an increased neuronal density, by reduced size of neuronal cell bodies and of the somatodendritic compartment of pyramidal neurons in the cortex. No evidence for apoptosis was obtained. The marked overall reduction in the level of the microtubule-associated protein 2 in brain and in spinal cord, did not affect the ultrastructure of the microtubular cytoskeleton in the proximal apical dendrites. The overall reduction in size of the entire CNS induced by constitutive active GSK-3beta caused only very subtle changes in the psychomotoric ability of adult and ageing GSK-3beta transgenic mice.

Animals↗

PubMed2002

Increased Trypanosoma cruzi invasion and heart fibrosis associated with high transforming growth factor beta levels in mice deficient in alpha(2)-macroglobulin.

Trypanosoma cruzi proteinases are involved in host cell invasion in human patients and in mouse models. In mice, murine alpha(2)-macroglobulin (MAM) and murinoglobulin are circulating plasma proteinase inhibitors that also have important roles in inflammation and immune modulation. To define their role in experimental Chagas disease, we investigated the susceptibility to T. cruzi infection of mice that are deficient only in alpha2-macroglobulins (AM-KO) or in both MAM and monomeric murinoglobulin-1 (MM-KO), relative to the wild type (WT). Despite the high parasite load, parasitemia was lower in AM-KO and MM-KO mice than in WT mice. Nevertheless, we observed a significantly higher parasite load in the hearts of AM-KO and MM-KO mice, i.e., more amastigote nests and inflammatory infiltrates than in WT mice. This result demonstrates a protective role for MAM in the acute phase of murine T. cruzi infection. We further demonstrated in vitro that human alpha2-macroglobulins altered the trypomastigote morphology and motility in a dose-dependent way, and that also impaired T. cruzi invasion in cardiomyocytes. Finally, we demonstrated that the levels of transforming growth factor beta in AM-KO mice increased significantly in the third week postinfection, concomitant with high amastigote burden and important fibrosis. Combined, these in vivo and in vitro findings demonstrate that the MAM contribute to the resistance of mice to acute myocarditis induced by experimental T. cruzi infection.

Animals↗

PubMed2001

Sequencing of the coding exons of the LRP1 and LDLR genes on individual DNA samples reveals novel mutations in both genes.

Five coding polymorphisms in de LRP1 gene, i.e. A217V, A775P, D2080N, D2632E and G4379S were discovered by sequencing its 89 exons in three test-groups of 22 healthy individuals, 29 Alzheimer patients and 18 individuals with different clinical and molecularly uncharacterized lipid metabolism problems. No genetic defect was evident in the LRP1 gene of any of the Alzheimer's disease (AD) patients, further excluding LRP1 as a major genetic problem in AD. Lipoprotein receptor related protein (LRP) A217V (exon 6) was clearly present in all groups as a polymorphism, while D2632E was observed only once in a healthy volunteer. On the other hand, LRP1 alleles A775P, D2080N, and G4379 were encountered only in patients with FH or with undefined problems of lipid metabolism. This finding forced one to also analyze the LDL receptor (LDLR) gene, for which a method was devised to sequence the entire region comprising LDLR exons 2-18. The resulting sequence contig of 33567 nucleotides yielded finally an exact physical map that corrects published and listed LDLR gene maps in many positions. In addition, next to known mutations in LDLR that cause FH, four novel LDLR defects were defined, i.e. del e7-10, exon 9 mutation N407T, a 20 bp insertion in exon 4, and a double mutation C292W/K290R in exon 6. No evidence for pathology connected to the LRP1 'mutations' was obtained by subsequent screening for the five LRP1 variants in larger groups of 110 FH patients and 118 patients with molecularly undefined, clinical problems of cholesterol and/or lipid metabolism. In three individuals with a mutant LDLR gene a variant LRP1 allele was also present, but without direct, obvious clinical compound effects, indicating that the variant LRP1 alleles must, for the present, be considered polymorphisms.

Adolescent↗

PubMed2001

Mutant presenilins disturb neuronal calcium homeostasis in the brain of transgenic mice, decreasing the threshold for excitotoxicity and facilitating long-term potentiation.

Mutant human presenilin-1 (PS1) causes an Alzheimer's-related phenotype in the brain of transgenic mice in combination with mutant human amyloid precursor protein by means of increased production of amyloid peptides (Dewachter, I., Van Dorpe, J., Smeijers, L., Gilis, M., Kuiperi, C., Laenen, I., Caluwaerts, N., Moechars, D., Checler, F., Vanderstichele, H. & Van Leuven, F. (2000) J. Neurosci. 20, 6452-6458) that aggravate plaques and cerebrovascular amyloid (Van Dorpe, J., Smeijers, L., Dewachter, I., Nuyens, D., Spittaels, K., van den Haute, C., Mercken, M., Moechars, D., Laenen, I., Kuipéri, C., Bruynseels, K., Tesseur, I., Loos, R., Vanderstichele, H., Checler, F., Sciot, R. & Van Leuven, F. (2000) J. Am. Pathol. 157, 1283-1298). This gain of function of mutant PS1 is approached here in three paradigms that relate to glutamate neurotransmission. Mutant but not wild-type human PS1 (i) lowered the excitotoxic threshold for kainic acid in vivo, (ii) facilitated hippocampal long-term potentiation in brain slices, and (iii) increased glutamate-induced intracellular calcium levels in isolated neurons. Prominent higher calcium responses were triggered by thapsigargin and bradykinin, indicating that mutant PS modulates the dynamic release and storage of calcium ions in the endoplasmatic reticulum. In reaction to glutamate, overfilled Ca(2+) stores resulted in higher than normal cytosolic Ca(2+) levels, explaining the facilitated long-term potentiation and enhanced excitotoxicity. The lowered excitotoxic threshold for kainic acid was also observed in mice transgenic for mutant human PS2[N141I] and was prevented by dantrolene, an inhibitor of Ca(2+) release from the endoplasmic reticulum.

Animals↗

PubMed2001

Coexpression of human cdk5 and its activator p35 with human protein tau in neurons in brain of triple transgenic mice.

The potential contribution of cyclin-dependent protein kinase 5 (cdk5) to hyperphosphorylate protein tau, as claimed in Alzheimer's disease, was investigated in vivo. We generated single, double, and triple transgenic mice that coexpress human cdk5 and its activator p35 as well as human protein tau in cerebral neurons. Whereas expression and increased cdk5-kinase activity was obtained, as measured in vitro and demonstrated in vivo, neither murine nor human protein tau was appreciably phosphorylated in the brain of double and triple transgenic mice. These mice behaved and reproduced normally. Silver impregnation and immunohistochemistry of brain sections demonstrated that neurofilament proteins became redistributed in apical dendrites of cortical neurons. This suggested a cytoskeletal effect, but no other relevant brain pathology became apparent. These observations indicate that cdk5/p35 is not a major protein tau kinase and that cdk5/p35 did not cause neurodegeneration in mouse brain, as opposed to cdk5/p25.

Animals↗

PubMed2001

The use of Achilles tendon ultrasonography for the diagnosis of familial hypercholesterolemia.

Differentiating FH from other causes of hypercholesterolemia has important clinical and therapeutic implications but is often not possible by standard clinical criteria. As accumulation of cholesterol in tendon is generally considered as pathognomonic of FH, we evaluated the sensitivity and specificity of clinical and ultrasonographic tendon characteristics using the data of 127 genetically ascertained FH and 160 controls with various lipid profiles. Upon clinical examination, none of the controls and 29% of FH individuals (17% FH women and 38% FH men) presented with xanthomata in Achilles tendons, but no female and only 6% of male FH patients also showed xanthomata in the extensor tendon of the hand. Amongst all possible quantitative parameters (thickness, breadth, section and roundness) of Achilles tendon (AT) measured by ultrasonography, the thickness presented the best receiver operating curves. AT thickness above 5.8 mm was the most useful threshold for diagnosis of FH, procuring sensitivity of 75% and specificity of 85%. Analysis of variation of AT thickness with age and sex indicated that this clinical criterion performed better in females older than 45 and in males under 45. In patients carrying the APOB-R3500Q mutation, AT-thickness appeared significantly less important compared with those carrying LDLR mutations. In conclusion, this study recommends identification of possible FH individuals amongst hypercholesterolemic patients using a criteria of AT-thickness over 5.8 mm eventually associated with a specific genetic test for APOB-R3500Q mutation.

Achilles Tendon↗

PubMed2001

Modelling Alzheimer's disease in multiple transgenic mice.

We have reported transgenic mice with neuronal overexpression of the clinical mutant beta-amyloid precursor protein (APP) known as London, which develop an AD-related phenotype [Moechers, Dewachter, Lorent, Reversé, Baekelandt, Nadiu, Tesseur, Spittaels, Van den Haute, Checler, et al. (1999) J. Biol. Chem. 274, 6483-6492]. Characterized early symptoms (3-9 months) include disturbed behaviour, neophobia, aggression, hypersensitivity to kainic acid, hyposensitivity to N-methyl-D-aspartate, defective cognition and memory, and decreased long-term potentiation. Late in life, at 12-15 months, amyloid plaques develop in the brain and correlate with increased levels of beta-amyloid (A beta)40/42 (the 40- and 42-amino-acid forms of A beta). The formation of amyloid plaques is dissociated in time from and not involved in the early phenotype. Hyperphosphorylated protein tau is present but no tangle pathology is observed. In double-transgenic mice, i.e. APP/London x Presenilin 1, the increased production of A beta 42 results in amyloid plaques developing by the age of 6 months. Transgenic mice with overexpression of either human apolipoprotein E4 (ApoE4) or human protein tau in central neurons develop severe axonopathy in the brain and spinal cord. Progressive degeneration of nerves and muscles is demonstrated by motor problems, wasting and premature death. Tau is hyperphosphorylated but there is no formation of filaments or neurofibrillary tangles. The tangle aspect of AD pathology is still missing from all current transgenic amyloid models. Its implementation will require insight into the cellular signalling pathways which regulate the microtubule-stabilizing function by phosphorylation of neuronal tau.

Alzheimer Disease↗

PubMed2001

Impact of genetic defects on atherosclerosis in patients suspected of familial hypercholesterolaemia.

BACKGROUND: Among patients with severe hypercholesterolaemia and a family history of early cardiovascular disease, we assessed whether patients with mutations of low-density lipoprotein (LDL) receptor and apolipoprotein B genes related to familial hypercholesterolaemia (FH) have a different degree of atherosclerosis than those without such mutations. METHOD: In our lipid clinics, 273 patients were selected on the basis of a severe hypercholesterolaemia (cholesterol above 95th percentile) and a family history of early cardiovascular disease. By molecular genetic test, 122 patients were classified as FH. Atherosclerosis was evaluated by the ultrasonographic measurement of intima-media thickness (IMT) in the carotid and femoral arteries. RESULT: Despite the fact that non-FH individuals had a higher prevalence of obesity, hypertension, diabetes and hypertriglyceridaemia, FH individuals had significantly greater carotid and femoral IMT than non-FH patients: difference between carotid and femoral IMT, respectively, 0.19 mm (95% CI, 0.08-0.29; P < 0.001) and 0.20 mm (95% CI, 0.09-0.35; P = 0.001), respectively. These differences remained statistically significant after adjustment for the various risk factors as well as in sub-analysis restricted to the patients with LDL-cholesterol between 240 and 300 mg dL-1 (range with similar distribution in the two groups). When classified according to the severity of their mutations, FH individuals with null LDL receptor allele tended to have thicker carotid IMT than FH individuals carrying the LDL receptor-defective allele. CONCLUSION: Among patients with severe hypercholesterolaemia and a family history of early cardiovascular disease, the presence of a genetically ascertained FH is associated with a higher degree of atherosclerosis. This suggests that molecular genetic identification of FH may be helpful to evaluate better the coronary heart disease risk in these patients.

Adult↗

PubMed2001

Differential expression of mRNA coding for the alpha-2-macroglobulin family and the LRP receptor system in C57BL/6J and C3H/HeJ male mice.

Expression of mouse A2M (MAM), murinoglobulin (MUG), the A2M receptor or LDL-Receptor related protein (A2MR/LRP) and the Receptor Associated Protein (RAP) were measured by northern blotting of mRNA isolated from liver, heart and peritoneal macrophages from C3H/HeJ and C57BL/6J (B6) mice. Marked differences between males of the two mouse strains were observed for MAM and MUG mRNA levels in liver, which were reflected in plasma levels of both proteinase inhibitors, as confirmed by immune-electrophoresis. C3H/HeJ mice had higher levels of the MAM and MUG mRNA and their corresponding plasma proteins than B6 mice. B6 mice expressed higher levels of LRP mRNA relative to C3H/HeJ mice but had lower levels of RAP mRNA. LRP receptor activity, assayed by fluoresceinated-A2M binding, was higher in B6 cells. The present data contribute to the knowledge of genetic background characteristics among male mouse of these two strains, which can take part in many biological events such as lipid metabolism, inflammation and immune response to different infectious agents.

Animals↗

PubMed2000

Glycogen synthase kinase-3beta phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice.

Protein tau filaments in brain of patients suffering from Alzheimer's disease, frontotemporal dementia, and other tauopathies consist of protein tau that is hyperphosphorylated. The responsible kinases operating in vivo in neurons still need to be identified. Here we demonstrate that glycogen synthase kinase-3beta (GSK-3beta) is an effective kinase for protein tau in cerebral neurons in vivo in adult GSK-3beta and GSK-3beta x human tau40 transgenic mice. Phosphorylated protein tau migrates slower during electrophoretic separation and is revealed by phosphorylation-dependent anti-tau antibodies in Western blot analysis. In addition, its capacity to bind to re-assembled paclitaxel (Taxol((R)))-stabilized microtubules is reduced, compared with protein tau isolated from mice not overexpressing GSK-3beta. Co-expression of GSK-3beta reduces the number of axonal dilations and alleviates the motoric impairment that was typical for single htau40 transgenic animals (Spittaels, K., Van den Haute, C., Van Dorpe, J., Bruynseels, K., Vandezande, K., Laenen, I., Geerts, H., Mercken, M., Sciot, R., Van Lommel, A., Loos, R., and Van Leuven, F. (1999) Am. J. Pathol. 155, 2153-2165). Although more hyperphosphorylated protein tau is available, neither an increase in insoluble protein tau aggregates nor the presence of paired helical filaments or tangles was observed. These findings could have therapeutic implications in the field of neurodegeneration, as discussed.

Alzheimer Disease↗

PubMed2000

Aging increased amyloid peptide and caused amyloid plaques in brain of old APP/V717I transgenic mice by a different mechanism than mutant presenilin1.

Aging of transgenic mice that overexpress the London mutant of amyloid precursor protein (APP/V717I) (Moechars et al., 1999a) was now demonstrated not to affect the normalized levels of alpha- or beta-cleaved secreted APP nor of the beta-C-terminal stubs. This indicated that aging did not markedly disturb either alpha- or beta-secretase cleavage of APP and failed to explain the origin of the massive amounts of amyloid peptides Abeta40 and Abeta42, soluble and precipitated as amyloid plaques in the brain of old APP/V717I transgenic mice. We tested the hypothesis that aging acted on presenilin1 (PS1) to affect gamma-secretase-mediated production of amyloid peptides by comparing aged APP/V717I transgenic mice to double transgenic mice coexpressing human PS1 and APP/V717I. In double transgenic mice with mutant (A246E) but not wild-type human PS1, brain amyloid peptide levels increased and resulted in amyloid plaques when the mice were only 6-9 months old, much earlier than in APP/V717I transgenic mice (12-15 months old). Mutant PS1 increased mainly brain Abeta42 levels, whereas in aged APP/V717I transgenic mice, both Abeta42 and Abeta40 increased. This resulted in a dramatic difference in the Abeta42/Abeta40 ratio of precipitated or plaque-associated amyloid peptides, i.e., 3.11+/-0.22 in double APP/V717I x PS1/A246E transgenic mice compared with 0.43 +/- 0.07 in aged APP/V717I transgenic mice, and demonstrated a clear difference between the effect of aging and the effect of the insertion of a mutant PS1 transgene. In conclusion, we demonstrate that aging did not favor amyloidogenic over nonamyloidogenic processing of APP, nor did it exert a mutant PS1-like effect on gamma-secretase. Therefore, the data are interpreted to suggest that parenchymal and vascular accumulation of amyloid in aging brain resulted from failure to clear the amyloid peptides rather than from increased production.

Aging↗

PubMed2000

Abnormal glutamate transport function in mutant amyloid precursor protein transgenic mice.

Recent studies have shown that amyloid precursor protein (APP), which plays a central role in Alzheimer's disease (AD), protects against excitotoxic neuronal injuries by regulating the function of the glial glutamate transporters. The mechanisms underlying these effects and their relationship to the neurodegenerative process in AD are under intense scrutiny. In this context, the main objective of the present study was to determine if overexpression of mutant human APP in transgenic mouse brains results in altered functioning of the excitatory amino acid transporters (EAATs). Transgenic mice expressing the 695 amino acid form of the human APP from the Thy-1 promoter showed a significant decrease in B(max) and K(D) for aspartate uptake when compared to nontransgenic controls. This decrease in glutamate transporter activity was associated with decreased protein expression of glial specific glutamate transporters, EAAT1 and 2, but did not affect mRNA levels. These results suggest that expression of mutant forms of APP disturbs astroglial transport of excitatory amino acids at the posttranscriptional level leading, in turn, to increased susceptibility to glutamate toxicity.

ATP-Binding Cassette Transporters↗

PubMed2000

Trypanosoma cruzi: acute infection affects expression of alpha-2-macroglobulin and A2MR/LRP receptor differently in C3H and C57BL/6 mice.

Although a complete cellular and humoral immune response is elicited in Chagas' disease, recent data suggest that other natural elements of innate immunity may also contribute to the initial host primary defense. alpha-Macroglobulins are a family of plasma proteinase inhibitors that are acute-phase reactants in Trypanosoma cruzi-infected mice and humans. Mice contain a tetrameric alpha-2-macroglobulin (MAM) and a monomeric murinoglobulin (MUG). Heterogeneity in their reactions was observed in murine T. cruzi-infected plasma A2M levels despite an overall increase. In addition, up-regulation of the A2M receptor (A2MR/LRP) was observed in peritoneal macrophages during T. cruzi infection. Here, we show that during T. cruzi infection (Y strain), the MAM and MUG hepatic mRNA levels and the corresponding plasma protein levels were up-regulated in C3H and C57BL/6 (B6) mice, but with different kinetics. On the contrary, A2MR/LRP mRNA levels increased in acutely infected C3H mice, but decreased in B6 mice, in both liver and heart. Immunocytochemistry of infected B6 heart cryosections confirmed a less intense endothelium labeling by the fluoresceinated ligand for A2MR/LRP. On the other hand, infected B6 spleen cells displayed higher F-A2M-FITC binding and MAC1 expression, confirming higher A2MR/LRP expression in macrophages. In uninfected mice, as well as after T. cruzi infection, higher A2M plasma levels were measured in C3H mice than in B6 mice. The lower tissue T. cruzi parasitism found in C3H-infected mice could reflect an inhibitory effect of A2M on parasite invasion. Our present data further contribute to clarifying aspects of the role of A2MR/LRP in a model of acute Chagas' disease in different mouse strains.

Acute Disease↗

PubMed2000

Behavioral disturbances without amyloid deposits in mice overexpressing human amyloid precursor protein with Flemish (A692G) or Dutch (E693Q) mutation.

The contribution of mutations in the amyloid precursor protein (APP) gene known as Flemish (APP/A692G) and Dutch (APP/E693Q) to the pathogenesis of Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis of the Dutch type, respectively, was studied in transgenic mice that overexpress the mutant APP in brain. These transgenic mice showed the same early behavioral disturbances and defects and increased premature death as the APP/London (APP V717I), APP/Swedish (K670N, M671L), and other APP transgenic mice described previously. Pathological changes included intense glial reaction, extensive microspongiosis in the white matter, and apoptotic neurons in select areas of the brain, while amyloid deposits were absent, even in mice over 18 months of age. This contrasts with extensive amyloid deposition in APP/London transgenic mice and less pronounced amyloid deposition in APP/Swedish transgenic mice generated identically. It demonstrated, however, that the behavioral deficiencies and the pathological changes in brain resulting from an impaired neuronal function are caused directly by APP or its proteolytic derivative(s). These accelerate or impinge on the normal process of aging and amyloid deposits per se are not essential for this phenotype.

Aggression↗

PubMed2000

Acetylcholinesterase-positive fiber deafferentation and cell shrinkage in the septohippocampal pathway of aged amyloid precursor protein london mutant transgenic mice.

Several lines of evidence implicate a cholinergic deficit in Alzheimer's disease (AD). Transgenic mice that overexpress clinical mutants of the human amyloid precursor protein (APP) have been generated that recapitulate many aspects of AD. We now analyzed the cholinergic system in aged APP/London transgenic mice. The major finding was the reorganization of acetylcholinesterase-positive fibers within the hippocampus and the reduced size of cholinergic cells in the medial septum. The reduction of acetylcholinesterase-positive fibers in the subiculum together with increased fiber density in the CA1 and in the dentate gyrus suggests a synaptic sprouting compensatory mechanism within the hippocampus. In the cortex, amyloid plaques were associated with intense acetylcholinesterase activity and surrounded by dystrophic acetylcholinesterase-positive fibers. Nevertheless, the overall pattern of cholinergic innervation was unchanged. These results demonstrate that overexpression of APP/London caused, besides amyloid plaques in aged mouse brain, also cholinergic deafferentation and cholinergic cell shrinkage.

Acetylcholinesterase↗

PubMed2000

Fruit-specific lectins from banana and plantain.

One of the predominant proteins in the pulp of ripe bananas (Musa acuminata L.) and plantains (Musa spp.) has been identified as a lectin. The banana and plantain agglutinins (called BanLec and PlanLec, respectively) were purified in reasonable quantities using a novel isolation procedure, which prevented adsorption of the lectins onto insoluble endogenous polysaccharides. Both BanLec and PlanLec are dimeric proteins composed of two identical subunits of 15 kDa. They readily agglutinate rabbit erythrocytes and exhibit specificity towards mannose. Molecular cloning revealed that BanLec has sequence similarity to previously described lectins of the family of jacalin-related lectins, and according to molecular modelling studies has the same overall fold and three-dimensional structure. The identification of BanLec and PlanLec demonstrates the occurrence of jacalin-related lectins in monocot species, suggesting that these lectins are more widespread among higher plants than is actually believed. The banana and plantain lectins are also the first documented examples of jacalin-related lectins, which are abundantly present in the pulp of mature fruits but are apparently absent from other tissues. However, after treatment of intact plants with methyl jasmonate, BanLec is also clearly induced in leaves. The banana lectin is a powerful murine T-cell mitogen. The relevance of the mitogenicity of the banana lectin is discussed in terms of both the physiological role of the lectin and the impact on food safety.

Amino Acid Sequence↗