Laminin inhibits amyloid-β-peptide fibrillation

Bronfman, Francisca C.; Garrido, Jorge; Álvarez, Alejandra; Morgan, Carlos; Inestrosa, Nibaldo C.

doi:10.1016/s0304-3940(96)13147-5

Cited by 64 publications

(45 citation statements)

References 17 publications

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“…6 As Ab is toxic to neurons, 7 the main targets for therapeutic intervention of the Ab cascade include the inhibition of Ab production, the inhibition of Ab aggregation and fibril formation, in addition to the inhibition of the consequent inflammatory responses caused by the Ab deposition. In this context, several substances are known to inhibit Ab fibrillogenesis in vitro, including laminin, 6,8 melatonin, 9 nordihydroguaiaretic acid, 10 polyphenols, 11 site-directed monoclonal antibodies, 12 a1-antichymotrypsin, 13 Ginkgo biloba extract, 14 type IV collagen 15 and b-sheet breaker peptides. 16 Nevertheless, an effective therapeutic approach that interferes directly with the neurodegenerative process in AD is eagerly awaited.…”

Section: Introductionmentioning

confidence: 99%

Hyperforin prevents β-amyloid neurotoxicity and spatial memory impairments by disaggregation of Alzheimer's amyloid-β-deposits

Dinamarca¹,

Cerpa²,

Garrido

et al. 2006

Mol Psychiatry

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The major protein constituent of amyloid deposits in Alzheimer's disease (AD) is the amyloid b-peptide (Ab). In the present work, we have determined the effect of hyperforin an acylphloroglucinol compound isolated from Hypericum perforatum (St John's Wort), on Ab-induced spatial memory impairments and on Ab neurotoxicity. We report here that hyperforin: (1) decreases amyloid deposit formation in rats injected with amyloid fibrils in the hippocampus; (2) decreases the neuropathological changes and behavioral impairments in a rat model of amyloidosis; (3) prevents Ab-induced neurotoxicity in hippocampal neurons both from amyloid fibrils and Ab oligomers, avoiding the increase in reactive oxidative species associated with amyloid toxicity. Both effects could be explained by the capacity of hyperforin to disaggregate amyloid deposits in a dose and time-dependent manner and to decrease Ab aggregation and amyloid formation. Altogether these evidences suggest that hyperforin may be useful to decrease amyloid burden and toxicity in AD patients, and may be a putative therapeutic agent to fight the disease.

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Section: Introductionmentioning

confidence: 99%

Hyperforin prevents β-amyloid neurotoxicity and spatial memory impairments by disaggregation of Alzheimer's amyloid-β-deposits

Dinamarca¹,

Cerpa²,

Garrido

et al. 2006

Mol Psychiatry

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“…[4][5][6][7][8] However, the clinic study was halted because the human vaccination induced a severe brain inflammatory response, 9,10 which can be related to cerebral hemorrhages observed after passive anti-Ab immunotherapy in APP23 transgenic mice. 11 In addition, several molecules have been used either to inhibit polymerization of Ab peptides or to disaggregate Ab fibrils, including laminin 12,13 melatonin, 14 nordihydroguaiaretic acid, 15 polyphenols, 16 site-directed monoclonal antibodies, 17 a 1 -antichymotrypsin, 18 fullerene, 19 Ginkgo biloba extract, 20 type IV collagen, 21 short Ab congeners 22 and b-sheet breaker peptides. [23][24][25] b-sheet breaker peptides have both a similar sequence to the middle region of Ab peptide and degree of hydrophobicity, but have a very low propensity to adopt a b-sheet conformation, which is responsible for the aggregation properties and the consequent neurotoxicity.…”

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confidence: 99%

β-sheet breaker peptide prevents Aβ-induced spatial memory impairments with partial reduction of amyloid deposits

et al. 2004

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Current evidence supports the notion that b-amyloid deposits or Ab intermediates may be responsible for the pathogenesis in Alzheimer's disease (AD) patients. In the present work, we have assessed the neuroprotective effect of the chronic intraperitoneal administration of a five-amino-acid b-sheet breaker peptide (iAb5p) on the rat behavioral deficit induced by the intrahippocampal Ab-fibrils injection. At 1 month after the injection, animals showed a partial reduction of the amyloid deposits formed and a decreased astrocytic response around the injection site. More importantly, we report that following the iAb5p treatment, hippocampaldependent spatial learning paradigms, including the standard Morris water maze and a working memory analysis, showed a significant prevention from impairments induced by Ab deposits in the dorsal hippocampus. Thus, it is possible that a noninvasive treatment such as the one presented here with b-sheet breaker peptides may be used as a potential therapy for AD patients. Molecular Psychiatry (2004) 9, 953-961.

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“…A␤ has been found to bind to several components of the extracellular matrix (ECM), including laminin (Bronfman et al, 1996) and proteoglycans (Snow et al, 1989;Fraser et al, 1992;Buée et al, 1993;Narindrasorasak et al, 1995;Castillo et al, 1997). As the ECM is important for the regulation of cell adhesion, axonal growth, and synaptogenesis during wound repair or synaptic remodeling (Venstrom and Reichardt, 1993;Letourneau et al, 1994;Small et al, 1996), this raises the possibility that A␤ could alter cell-cell or cell-substrate interactions in vivo.…”

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confidence: 99%

Substrate‐Bound β‐Amyloid Peptides Inhibit Cell Adhesion and Neurite Outgrowth in Primary Neuronal Cultures

Postuma

Nunan

et al. 2000

Journal of Neurochemistry

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Accumulation of the ␤-amyloid protein (A␤) in the brain is an important step in the pathogenesis of Alzheimer's disease. However, the mechanism of A␤ toxicity remains unclear. A␤ can bind to the extracellular matrix, a structure that regulates adhesive events such as neurite outgrowth and synaptogenesis. The binding of A␤ to the extracellular matrix suggests that A␤ may disrupt cell-substrate interactions. Therefore, the effect of substrate-bound A␤ on the growth of isolated chick sympathetic and mouse cortical neurons was examined. A␤1-40 and A␤1-42 had dose-dependent effects on cell morphology. When tissue culture plates were coated with 0.1-10 ng/well A␤, neurite outgrowth increased. Higher amounts of A␤ peptides (Ն3 g/well) inhibited outgrowth. The inhibitory effect was related to aggregation of the peptide, as preincubation of A␤1-40 for 24 h at 37°C (a process known to increase amyloid fibril formation) was necessary for inhibition of neurite outgrowth. A␤29 -42, but not A␤1-28, also inhibited neurite outgrowth at high concentrations, demonstrating that the inhibitory domain is located within the hydrophobic C-terminal region. A␤1-40, A␤1-42, and A␤29 -42 also inhibited cell-substrate adhesion, indicating that the effect on neurite outgrowth may have been due to inhibition of cell adhesion. The results suggest that accumulation of A␤ may disrupt celladhesion mechanisms in vivo.

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Laminin inhibits amyloid-β-peptide fibrillation

Cited by 64 publications

References 17 publications

Hyperforin prevents β-amyloid neurotoxicity and spatial memory impairments by disaggregation of Alzheimer's amyloid-β-deposits

Hyperforin prevents β-amyloid neurotoxicity and spatial memory impairments by disaggregation of Alzheimer's amyloid-β-deposits

β-sheet breaker peptide prevents Aβ-induced spatial memory impairments with partial reduction of amyloid deposits

Substrate‐Bound β‐Amyloid Peptides Inhibit Cell Adhesion and Neurite Outgrowth in Primary Neuronal Cultures

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