Focal adhesions regulate Aβ signaling and cell death in Alzheimer's disease

Caltagarone, John; Zheng, Jing; Bowser, Robert

doi:10.1016/j.bbadis.2006.11.007

Cited by 81 publications

(68 citation statements)

References 72 publications

(240 reference statements)

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“…We studied SH-SY5Y cells as a model system for their particular sensitivity to environmental stimuli (25,26) and for the importance of functional biomaterials in neural research. To obtain a good control of surface topography, we exploited a wet chemistry approach (SGDR) (27), achieving different nanorough gold surfaces (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Neural cells are known to be strongly affected by the properties of culture substrates (24). In particular, the SH-SY5Y cell line is a good model for neuronal differentiation and shows an integrin receptors pathway highly sensitive to environmental stimuli (25,26). To evaluate the effects that surface nanoroughness may exert over these neuronal cells, we applied a wet chemistry technique, namely, spontaneous galvanic displacement reactions (SGDR) (27) that can allow an extremely precise control over the surface morphology.…”

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confidence: 99%

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Neurons sense nanoscale roughness with nanometer sensitivity

Brunetti

Maiorano

Rizzello

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

232

213

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The interaction between cells and nanostructured materials is attracting increasing interest, because of the possibility to open up novel concepts for the design of smart nanobiomaterials with active biological functionalities. In this frame we investigated the response of human neuroblastoma cell line (SH-SY5Y) to gold surfaces with different levels of nanoroughness. To achieve a precise control of the nanoroughness with nanometer resolution, we exploited a wet chemistry approach based on spontaneous galvanic displacement reaction. We demonstrated that neurons sense and actively respond to the surface nanotopography, with a surprising sensitivity to variations of few nanometers. We showed that focal adhesion complexes, which allow cellular sensing, are strongly affected by nanostructured surfaces, leading to a marked decrease in cell adhesion. Moreover, cells adherent on nanorough surfaces exhibit loss of neuron polarity, Golgi apparatus fragmentation, nuclear condensation, and actin cytoskeleton that is not functionally organized. Apoptosis/necrosis assays established that nanoscale features induce cell death by necrosis, with a trend directly related to roughness values. Finally, by seeding SH-SY5Y cells onto micropatterned flat and nanorough gold surfaces, we demonstrated the possibility to realize substrates with cytophilic or cytophobic behavior, simply by fine-tuning their surface topography at nanometer scale. Specific and functional adhesion of cells occurred only onto flat gold stripes, with a clear self-alignment of neurons, delivering a simple and elegant approach for the design and development of biomaterials with precise nanostructuretriggered biological responses.nanobiointeractions | nanostructures | patterning T he potential of nanomaterials to trigger specific cellular responses, such as interference and/or activation of defined pathways (1-3), is promising for the development of many important scientific fields, such as regenerative medicine, biotechnology, drug delivery, and nanotoxicity assessment. Initially, cellsmaterials interactions were tackled only from a chemical point of view, because environmental sensing by cells involves specific binding between cellular receptors and ECM ligands. However, recently there has been increasing evidence that the biological response is also affected by the physical properties of the material (4). In particular, it has been demonstrated that cells are influenced by the substrate topography (5, 6), rigidity (7, 8), anisotropy (9, 10), surface charge (11, 12), and wettability (13,14). From this perspective, cellular response to external stimuli goes far beyond the bare ability of the cell to chemically sense specific ECM ligands and includes a wide range of physical cues that are generated at, or act on, the interface between cells and the surrounding environment. For instance, it has been observed that micrometer-scale roughness may affect cell proliferation and morphology (15,16), because it provides a quasi-biomimetic microenvironment to the cells. How...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Neurons sense nanoscale roughness with nanometer sensitivity

Brunetti

Maiorano

Rizzello

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

232

213

View full text Add to dashboard Cite

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“…In contrast, there is increasing evidence that integrins have a pathological role acting as potential neuronal and glia receptors mediating Aβ-induced cytotoxicity [42]. Soluble and fibrillar Aβ can substitute for extracellular matrix proteins and bind integrins, resulting in partial activation of focal adhesion signalling and, potentially, neurodegeneration [9,[43][44][45].…”

Section: The Cell Adhesion Molecule αV Integrin Mediates the Disruptimentioning

confidence: 95%

Synaptic memory mechanisms: Alzheimer's disease amyloid β-peptide-induced dysfunction

Rowan

Klyubin

Wang

et al. 2007

Biochemical Society Transactions

138

115

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There is growing evidence that mild cognitive impairment in early AD (Alzheimer's disease) may be due to synaptic dysfunction caused by the accumulation of non-fibrillar, oligomeric Abeta (amyloid beta-peptide), long before widespread synaptic loss and neurodegeneration occurs. Soluble Abeta oligomers can rapidly disrupt synaptic memory mechanisms at extremely low concentrations via stress-activated kinases and oxidative/nitrosative stress mediators. Here, we summarize experiments that investigated whether certain putative receptors for Abeta, the alphav integrin extracellular cell matrix-binding protein and the cytokine TNFalpha (tumour necrosis factor alpha) type-1 death receptor mediate Abeta oligomer-induced inhibition of LTP (long-term potentiation). Ligands that neutralize TNFalpha or genetic knockout of TNF-R1s (type-1 TNFalpha receptors) prevented Abeta-triggered inhibition of LTP in hippocampal slices. Similarly, antibodies to alphav-containing integrins abrogated LTP block by Abeta. Protection against the synaptic plasticity-disruptive effects of soluble Abeta was also achieved using systemically administered small molecules targeting these mechanisms in vivo. Taken together, this research lends support to therapeutic trials of drugs antagonizing synaptic plasticity-disrupting actions of Abeta oligomers in preclinical AD.

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“…It is the errant production of amyloid β peptides that is believed to lead to the formation of the characteristic amyloid plaques and neurofibrillary tangles within the neocortical and subcortical regions of the brain resulting in disease pathology. The γ secretase complex regulates production of these amyloid β peptides reviewed in (Caltagarone et al 2006;Zhou et al 2007). Recently CD147 was observed to be a regulatory component of the γ secretase complex (Zhou et al 2005).…”

Section: Alzheimer's Diseasementioning

confidence: 99%

CD147 immunoglobulin superfamily receptor function and role in pathology

Iacono

Brown

Greene

et al. 2007

Experimental and Molecular Pathology

245

206

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The immunoglobulin superfamily member CD147 plays an important role in fetal, neuronal, lymphocyte and extracellular matrix development. Here we review the current understanding of CD147 expression and protein interactions with regard to CD147 function and its role in pathologic conditions including heart disease, Alzheimer's disease, stroke and cancer. A model linking hypoxic conditions found within the tumor microenvironment to up-regulation of CD147 expression and tumor progression is introduced.

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Focal adhesions regulate Aβ signaling and cell death in Alzheimer's disease

Cited by 81 publications

References 72 publications

Neurons sense nanoscale roughness with nanometer sensitivity

Neurons sense nanoscale roughness with nanometer sensitivity

Synaptic memory mechanisms: Alzheimer's disease amyloid β-peptide-induced dysfunction

CD147 immunoglobulin superfamily receptor function and role in pathology

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