Identification and Immunolocalization of a New Class of Proteoglycan (Keratan Sulfate) to the Neuritic Plaques of Alzheimer's Disease

Snow, Alan D.; Nochlin, David; Sekiguchi, Raymond T.; Carlson, Steven S.

doi:10.1006/exnr.1996.0069

Cited by 80 publications

(43 citation statements)

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“…On SDS-PAGE the L form migrates like a protein of about 90 kDa, whereas the H form migrates with the characteristic heterogeneous mobility of a proteoglycan, between 90 and above 200 kDa (2). Both forms of SV2 appear to be present in vertebrate synapses, including those of electric fish (2), rat (2), and human (8). SV2 is also found in endocrine cells (1).…”

Section: Sv2mentioning

confidence: 99%

The Synaptic Vesicle Protein SV2 Is Complexed with an α5-Containing Laminin on the Nerve Terminal Surface

Son¹,

Scranton²,

Sunderland³

et al. 2000

Journal of Biological Chemistry

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Interactions between growing axons and synaptic basal lamina components direct the formation of neuromuscular junctions during nerve regeneration. Isoforms of laminin containing ␣5 or ␤2 chains are potential basal lamina ligands for these interactions. The nerve terminal receptors are unknown. Here we show that SV2, a synaptic vesicle transmembrane proteoglycan, is complexed with a 900-kDa laminin on synaptosomes from the electric organ synapse that is similar to the neuromuscular junctions. Although two laminins are present on synaptosomes, only the 900-kDa laminin is associated with SV2. Other nerve terminal components are absent from this complex. The 900-kDa laminin contains an ␣5, a ␤1, and a novel ␥ chain. To test whether SV2 directly binds the 900-kDa laminin, we looked for interaction between purified SV2 and laminin-1, a laminin isoform with a similar structure. We find SV2 binds with high affinity to purified laminin-1. Our results suggest that a synaptic vesicle component may act as a laminin receptor on the presynaptic plasma membrane; they also suggest a mechanism for activity-dependent adhesion at the synapse.

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Section: Sv2mentioning

confidence: 99%

The Synaptic Vesicle Protein SV2 Is Complexed with an α5-Containing Laminin on the Nerve Terminal Surface

Son¹,

Scranton²,

Sunderland³

et al. 2000

Journal of Biological Chemistry

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“…Several heparan sulfate proteoglycans have been found to codeposit with senile plaques and to interact with A␤ (12)(13)(14). Of particular interest is the binding of CLAC to heparin, suggesting that CLAC might have the potential to associate with other matrix or membrane-bound heparan sulfate proteoglycans.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, constituents of the extracellular brain matrix, e.g. the heparan sulfate proteoglycans (12)(13)(14), laminin (15,16), and collagen type IV (17), accumulate in amyloid plaques and bind to A␤. The appearance of some of these plaque-associated proteins may be indicative of a local inflammatory response to the amyloid, and others may promote A␤ aggregation or stabilize the amyloid plaques.…”

mentioning

confidence: 99%

Characterization of the Alzheimer's Disease-associated CLAC Protein and Identification of an Amyloid β-Peptide-binding Site

Söderberg

Kakuyama

Möller

et al. 2005

Journal of Biological Chemistry

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Amyloid ␤-peptide (A␤) deposition into amyloid plaques is one of the invariant neuropathological features of Alzheimer's disease. Other proteins co-deposit with A␤ in plaques, and one recently identified amyloidassociated protein is the collagen-like Alzheimer amyloid plaque component CLAC. It is not known how CLAC deposition affects A␤ plaque genesis and the progress of the disease. Here, we studied the in vitro properties of CLAC purified from a mammalian expression system. CLAC displays features characteristic of a collagen protein, e.g. it forms a partly protease-resistant triple-helical structure, exhibits an intermediate affinity for heparin, and is glycosylated. Purified CLAC was also used to investigate the interaction between CLAC and A␤. Using a solid-phase binding assay, we show that CLAC bound with a similar affinity to aggregates formed by A␤-(1-40) and A␤-(1-42) and that the interaction was impaired by increasing salt concentrations. An 8-residue-long sequence located in non-collagenous domain 2 of CLAC was found to be crucial for the interaction with A␤. These findings may be useful for future therapeutic interventions aimed at finding compounds that modulate the binding of CLAC to A␤ deposits.Alzheimer's disease (AD) 1 is a progressive neurodegenerative disorder characterized by selective neuronal loss associated with intracellular neurofibrillary tangle formation and extracellular amyloid plaques (1). The major constituents of the amyloid plaques are fibrils formed from the 40 -42-residue amyloid ␤-peptide (A␤) (2). A␤ is generated from the type I transmembrane Alzheimer amyloid precursor protein by two consecutive proteolytic cleavages. The aspartyl protease ␤-secretase BACE generates the N terminus of A␤, whereas the C terminus results from the proteolytic action of the ␥-secretase complex (3). Data from genetic and biochemical studies suggest that accumulation of the longer and more amyloidogenic species of A␤, A␤42, is a primary event in the development of AD (4). For instance, autosomal dominant forms of early-onset familial AD appear to result from an increased production of A␤42 (5), and total levels of brain A␤42 correlate with cognitive decline in AD (6).Several proteins other than A␤ have been shown by immunohistochemical methods to be associated with AD amyloid plaques (7). Some of these plaque-associated proteins, e.g. apolipoprotein J (8, 9), apolipoprotein E (10), and ␣ 1 -antichymotrypsin (11), modulate peptide aggregation. In addition, constituents of the extracellular brain matrix, e.g. the heparan sulfate proteoglycans (12-14), laminin (15, 16), and collagen type IV (17), accumulate in amyloid plaques and bind to A␤. The appearance of some of these plaque-associated proteins may be indicative of a local inflammatory response to the amyloid, and others may promote A␤ aggregation or stabilize the amyloid plaques. Recently, a novel plaque-associated protein, CLAC (collagen-like Alzheimer amyloid plaque component), was identified using antibodies raised against insoluble amyloid fr...

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“…The fact that Ab 1-40 induced a long lasting expression of CD44 on astrocytoma cells may have an important pathogenetic role, since CD44 through the binding to hyaluronic acid, proteoglycans and collagens may favour the accumulation of these products at plaque site (Snow et al, 1996;McLaurin et al, 1999;van Horssen et al, 2002). CD44-positive astrocytes will directly participate to the arrangement of the plaques.…”

Section: Discussionmentioning

confidence: 99%

“…It is not clear, however, whether beta-amyloid and its fragments modulate the expression of adhesion molecules or activation markers in human astrocytes, as well, thus participating to the amplification of the inflammatory response. Data in the literature indicate that CD44, a ligand for hyaluronic acid and other proteoglycans, is upregulated on the surface of astrocytes present near the vessel of senile plaques in AD patients (Akiyama et al, 1993;Kaaijk et al, 1996;Snow et al, 1996). Vascular cell adhesion molecule-1 (VCAM-1) is also overexpressed on neurons in AD upon amyloid stimulation (Du Yan et al, 1997) and induced by IL1b and TNFa on astrocytoma (Moynagh et al, 1994;Oh et al, 1998;Winkler and Benveniste, 1998;Bourke and Moynagh, 1999).…”

mentioning

confidence: 99%

1–40 β‐amyloid protein fragment modulates the expression of CD44 and CD71 on the astrocytoma cell line in the presence of IL1β and TNFα

Speciale

Ruzzante

Calabrese

et al. 2003

Journal Cellular Physiology

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The modulation of CD44, VCAM-1 and CD71 expression was analysed by flow cytometry in the 1321N1 astrocytoma cell line in the presence of interleukin-1b (IL1b), tumour necrosis factor-a (TNFa) and 1-40 or 25-35 b-amyloid (Ab) fragments. The percentage of 1321N1 astrocytoma cell line expressing these markers increased significantly after treatment with TNFa or IL1b. The presence of Ab 1-40 fragment, alone or in combination with IL1b, induced an increase in the percentage of cells expressing CD44, but not VCAM-1. However, the concomitant presence of Ab 1-40 fragment and of IL1b or TNFa caused an increase in the percentage of CD71 positive cells. In contrast, the shorter Ab 25-35 fragment was always inactive. These results indicates that Ab 1-40 fragment, in association with cytokines, can activate this astrocyte-derived cell line and add further elements in favour of the hypothesis that b-amyloid can act as immunological mediator.

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Identification and Immunolocalization of a New Class of Proteoglycan (Keratan Sulfate) to the Neuritic Plaques of Alzheimer's Disease

Cited by 80 publications

References 0 publications

The Synaptic Vesicle Protein SV2 Is Complexed with an α5-Containing Laminin on the Nerve Terminal Surface

The Synaptic Vesicle Protein SV2 Is Complexed with an α5-Containing Laminin on the Nerve Terminal Surface

Characterization of the Alzheimer's Disease-associated CLAC Protein and Identification of an Amyloid β-Peptide-binding Site

1–40 β‐amyloid protein fragment modulates the expression of CD44 and CD71 on the astrocytoma cell line in the presence of IL1β and TNFα

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