An important role of heparan sulfate proteoglycan (perlecan) in a model system for the deposition and persistence of fibrillar aβ-amyloid in rat brain

Snow, Alan D.; Sekiguchi, Raymond T.; Nochlin, David; Fraser, Paul E.; Kimata, Koji; Mizutani, Akihiro; Arai, Mamoru; Schreier, Wayne A.; Morgan, David

doi:10.1016/0896-6273(94)90165-1

Cited by 288 publications

(163 citation statements)

References 63 publications

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“…HSPG2 is expressed in basement membranes in several tissues, including brain. 55 It has been previously associated with Alzheimer's disease 56 and intracranial aneurysms. 57 As suggested by Syu et al, 30 its involvement in TD pathophysiology may be related to its influence on cholinergic transmission.…”

Section: Discussionmentioning

confidence: 99%

Support for association of HSPG2 with tardive dyskinesia in Caucasian populations

Greenbaum¹,

Alkelai²,

Zozulinsky³

et al. 2011

Pharmacogenomics J

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Tardive dyskinesia (TD) is a severe adverse effect of chronic antipsychotic drug treatment. In addition to clinical risk factors, TD susceptibility is influenced by genetic predisposition. Recently, Syu et al. (2010) reported a genome-wide association screening of TD in Japanese schizophrenia patients. The best result was association of single-nucleotide polymorphism (SNP) rs2445142 in the HSPG2 (heparan sulfate proteoglycan 2) gene with TD. In the present study, we report a replication study of the five top Japanese TDassociated SNPs in two Caucasian TD samples. Applying logistic regression and controlling for relevant clinical risk factors, we were able to replicate the association of HSPG2 SNP rs2445142 with TD in a prospective study sample of 179 Americans of European origin by performing a secondary analysis of the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) genome-wide association study data set, and using a perfect proxy surrogate marker (rs878949; P ¼ 0.039). An association of the 'G' risk allele of HSPG2 SNP rs2445142 with TD was also shown in a sample of Jewish Israeli schizophrenia patients (retrospective, cross-sectional design; P ¼ 0.03). Although the associations were only nominally significant, the findings provide further support for the possible involvement of HSPG2 in susceptibility to TD.

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Section: Discussionmentioning

confidence: 99%

Support for association of HSPG2 with tardive dyskinesia in Caucasian populations

Greenbaum¹,

Alkelai²,

Zozulinsky³

et al. 2011

Pharmacogenomics J

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“…A number of other macromolecules colocalize with A␤ in the plaque, including HSPGs (1,14). Over the years a body of experimental evidence has accumulated which indicates HSPGs play a role in the promotion, deposition, and persistence of the fibrillar form of A␤ present in plaques (1)(2)(3)14). HS glycosaminoglycans induce A␤ aggregation (3), cause A␤ fibers to form bundles (2), and protect the fibrillar A␤ from proteases (14).…”

Section: Discussionmentioning

confidence: 99%

“…A␤ binds to HSPGs with high affinity, and interestingly, it interacts with both the core protein and the glycosaminoglycan chains (3,4). Experiments by Snow et al (1) suggest that both interactions are necessary for the formation of fibrillar A␤-amyloid, since coinfusion of A␤ and HSPGs into rat brain produced deposits, whereas coinfusion of A␤ and HS glycosaminoglycans did not. This is somewhat surprising, since in vitro, HS chains alone can cause both A␤ and A␤(1-40) to aggregate (3), and heparin converts A␤ (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) into macrofibers (2).…”

mentioning

confidence: 99%

“…Histochemical and immunocytochemical studies have shown that heparan sulfate (HS) 1 proteoglycans (HSPGs) and glycosaminoglycans colocalize with ␤-amyloid protein (A␤) in the senile plaques characteristic of Alzheimer's disease (1). Although the precise role of the proteoglycans in the process of amyloidosis is not known, experimental evidence suggests that they may promote amyloid formation, deposition, and/or persistence (1) by binding to A␤ (2)(3)(4)(5).…”

mentioning

confidence: 99%

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Aβ(1–40) Prevents Heparanase-catalyzed Degradation of Heparan Sulfate Glycosaminoglycans and Proteoglycans in Vitro

Bame

Danda

Hassall

et al. 1997

Journal of Biological Chemistry

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Alzheimer's disease is characterized by senile plaques composed of polymeric fibrils of beta amyloid (A␤), a 39 -42-amino acid peptide formed after proteolytic processing of the amyloid precursor protein (␤APP). Heparan sulfate proteoglycans have been shown to colocalize with A␤ in Alzheimer's disease brain, and experimental evidence indicates that the interactions between the proteoglycan and the peptide are important for the promotion, deposition, and/or persistence of the senile plaques. Studies in rat brain indicated that both the core protein and the heparan sulfate glycosaminoglycan chains are required for amyloid fiber formation and deposition in vivo (Snow, A. D., Sekiguchi, R., Nochlin, D., Fraser, P., Kimata, K., Mizutani, A., Arai, M., Schreier, W. A., and Morgan, D. G. (1994) Neuron 12, 219 -234), suggesting that one mechanism to prevent the formation of A␤-heparan sulfate proteoglycan complexes that lead to deposition of amyloid would be to degrade the proteoglycan. Normally, heparan sulfate proteoglycans are internalized and degraded to short glycosaminoglycans by intracellular heparanases. These reactions occur in the endosomal-lysosomal pathway, which is the same intracellular location where ␤APP is processed to A␤. Using partially purified heparanase activities from Chinese hamster ovary cells we examined whether A␤(1-40) affects the catabolism of Chinese hamster ovary heparan sulfate glycosaminoglycans and proteoglycans in vitro. A␤(1-40) binds to both the long heparan sulfate glycosaminoglycans attached to core proteins and the short, heparanase-derived chains in a concentration-dependent and pH-dependent manner. When A␤(1-40) is added to heparanase assays, it prevents the partially purified activities from releasing heparan sulfate chains from core proteins and degrading them to short glycosaminoglycans; however, a large molar excess of the peptide to heparan sulfate is required to see the effect. Our results suggest that normally the levels of A␤ in the endosomal pathway are not sufficient to interfere with heparanase activity in vivo. However, once the level of A␤-peptides are elevated, as they are in Alzheimer's disease, they could interact with heparan sulfate proteoglycans and prevent their catabolism. This could promote the formation and deposition of amyloid, since the binding of A␤ to the proteoglycan species will predominate.Histochemical and immunocytochemical studies have shown that heparan sulfate (HS) 1 proteoglycans (HSPGs) and glycosaminoglycans colocalize with ␤-amyloid protein (A␤) in the senile plaques characteristic of Alzheimer's disease (1). Although the precise role of the proteoglycans in the process of amyloidosis is not known, experimental evidence suggests that they may promote amyloid formation, deposition, and/or persistence (1) by binding to A␤ (2-5). HSPGs are anionic molecules consisting of one or more HS glycosaminoglycan chains covalently attached to a core protein (6). A␤ binds to HSPGs with high affinity, and interestingly, it interacts with both the core pr...

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“…The occurrence of fibrils obviously evokes the occurrence pathological extracellular deposits of fibrillar β-amyloid and HSPGs. It is known that several HSPGs such as perlecan, agrin, glypican, syndecans 2 and 3, and collagen XVIII are found in senile plaques, ghost tangles and other deposits in Alzheimer disease (Snow et al 1994, Verbeek et al 1999, Van Horssen et al 2002. Furthermore, an electromicroscopical and immunocytochemistry study of brains affected by Alzheimer's disease has shown that certain Aβ -immunolabeled processes may contain GFAPreactive filaments (Kurt et al 1999).…”

Section: Non-neuronal Hspgs Modulation Of Neurite Growth At the Midlimentioning

confidence: 99%

Modulators of axonal growth and guidance at the brain midline with special reference to glial heparan sulfate proteoglycans

Cavalcante

Garcia-Abreu

Moura‐Neto

et al. 2002

An. Acad. Bras. Ciênc.

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Bilaterally symmetric organisms need to exchange information between the left and right sides of their bodies to integrate sensory input and to coordinate motor control. Thus, an important choice point for developing axons is the Central Nervous System (CNS) midline. Crossing of this choice point is influenced by highly conserved, soluble or membrane-bound molecules such as the L1 subfamily, laminin, netrins, slits, semaphorins, Eph-receptors and ephrins, etc. Furthermore, there is much circumstantial evidence for a role of proteoglycans (PGs) or their glycosaminoglycan (GAG) moieties on axonal growth and guidance, most of which was derived from simplified models. A model of intermediate complexity is that of cocultures of young neurons and astroglial carpets (confluent cultures) obtained from medial and lateral sectors of the embryonic rodent midbrain soon after formation of its commissures. Neurite production in these cocultures reveals that, irrespective of the previous location of neurons in the midbrain, medial astrocytes exerted an inhibitory or nonpermissive effect on neuritic growth that was correlated to a higher content of both heparan and chondroitin sulfates (HS and CS). Treatment with GAG lyases shows minor effects of CS and discloses a major inhibitory or non-permissive role for HS. The results are discussed in terms of available knowledge on the binding of HSPGs to interative proteins and underscore the importance of understanding glial polysaccharide arrays in addition to its protein complement for a better understanding of neuron-glial interactions.

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An important role of heparan sulfate proteoglycan (perlecan) in a model system for the deposition and persistence of fibrillar aβ-amyloid in rat brain

Cited by 288 publications

References 63 publications

Support for association of HSPG2 with tardive dyskinesia in Caucasian populations

Support for association of HSPG2 with tardive dyskinesia in Caucasian populations

Aβ(1–40) Prevents Heparanase-catalyzed Degradation of Heparan Sulfate Glycosaminoglycans and Proteoglycans in Vitro

Modulators of axonal growth and guidance at the brain midline with special reference to glial heparan sulfate proteoglycans

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