Spherulites in Human Brain Tissue are Composed of Beta Sheets of Amyloid and Resemble Senile Plaques

House, Emily; Jones, Krista; Exley, Christopher

doi:10.3233/jad-2011-110071

Cited by 16 publications

(22 citation statements)

References 13 publications

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“…Since then, further studies have been performed on insulin[12,44,45,50,101,102] and several even structurally unrelated proteins and peptides have been shown to have the same ability of forming in vitro spherulites in specific experimental conditions: A‐beta (1–42)[103], beta‐lactoglobulin[104], myelin basic protein (MBP)[105], a hexapeptide of human calcitonin[106], recombinant human interferon alpha‐2b[107], pro‐islet amyloid polypeptide ProIAPP(1–48)[108], whey protein mixtures[109] and Human Serum Albumin[110]. Moreover, beta‐sheet rich spherulites were observed in human brain tissues, resembling senile plaques associated with Alzheimer's disease[111], highlighting the potential involvement of such structures in the pathology. It is generally accepted that amyloid‐like spherulites are formed by a central densely packed part (referred as precursor ) and an external shell composed by radially growing amyloid fibrils[101].…”

Section: Assembly Into Complex Superstructures: Amyloid‐like Spherulimentioning

confidence: 99%

The route to protein aggregate superstructures: Particulates and amyloid‐like spherulites

Vetri

Foderà

2015

FEBS Letters

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a b s t r a c tDepending on external conditions, native proteins may change their structure and undergo different association routes leading to a large scale polymorphism of the aggregates. This feature has been widely observed but is not fully understood yet. This review focuses on morphologies, physico-chemical properties and mechanisms of formation of amyloid structures and protein superstructures. In particular, the main focus will be on protein particulates and amyloid-like spherulites, briefly summarizing possible experimental methods of analysis. Moreover, we will highlight the role of protein conformational changes and dominant forces in driving association together with their connection with the final aggregate structure. Eventually, we will discuss future perspectives in this field and we will comment what is, in our opinion, urgently needed.

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Section: Assembly Into Complex Superstructures: Amyloid‐like Spherulimentioning

confidence: 99%

The route to protein aggregate superstructures: Particulates and amyloid‐like spherulites

Vetri

Foderà

2015

FEBS Letters

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“…20 Spherulites are now recognized as not being a minor component within a protein aggregation reaction 20 and they are also reported in connection with Alzheimer´s disease. 21,22 The occurrence of this alternative structure appears to be regulated by electrostatics interactions. 17,20 The above facts change the paradigm that associates amyloid-like aggregation uniquely to the formation of elongated fibrils and pose new questions on the role of different PPIs in determining specific amyloid structures, being this knowledge pivotal for the disease´s etiology.…”

Section: Introductionmentioning

confidence: 99%

Ethanol Controls the Self-Assembly and Mesoscopic Properties of Human Insulin Amyloid Spherulites

et al. 2018

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Protein self-assembly into amyloid fibrils or highly hierarchical superstructures is closely linked to neurodegenerative pathologies as Alzheimer's and Parkinson's diseases. Moreover, protein assemblies also emerged as building blocks for bioinspired nanostructured materials. In both the above mentioned fields, the main challenge is to control the growth and properties of the final protein structure. This relies on a more fundamental understanding of how interactions between proteins can determine structures and functions of biomolecular aggregates. Here, we identify a striking effect of the hydration of the single human insulin molecule and solvent properties in controlling hydrophobicity/hydrophilicity, structures, and morphologies of a superstructure named spherulite, observed in connection to Alzheimer's disease. Depending on the presence of ethanol, such structures can incorporate fluorescent molecules with different physicochemical features and span a range of mechanical properties and morphologies. A theoretical model providing a thorough comprehension of the experimental data is developed, highlighting a direct connection between the intimate physical protein-protein interactions, the growth, and the properties of the self-assembled superstructures. Our findings indicate structural variability as a general property for amyloid-like aggregates and not limited to fibrils. This knowledge is pivotal not only for developing effective strategies against pathological amyloids but also for providing a platform to design highly tunable biomaterials, alternative to elongated protein fibrils.

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“…[33][34][35][36][37][38][39][40][41] In these structures, amyloid fibers grow radially from the center, where one may find an amorphous core. The existence, size, and, morphology of the amorphous core is dependent on the source protein and the conditions under which they are formed.…”

Section: Introductionmentioning

confidence: 99%

Label-free imaging of amyloids using their intrinsic linear and nonlinear optical properties

Johansson¹,

Koelsch²

2017

Biomed. Opt. Express

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The optical properties of amyloid fibers are often distinct from those of the source protein in its non-fibrillar form. These differences can be utilized for label-free imaging or characterization of such structures, which is particularly important for understanding amyloid fiber related diseases such as Alzheimer's and Parkinson's disease. We demonstrate that two amyloid forming proteins, insulin and β-lactoglobulin (β-LG), show intrinsic fluorescence with emission spectra that are dependent on the excitation wavelength. Additionally, a new fluorescence peak at about 430 nm emerges for β-LG in its amyloid state. The shift in emission wavelength is related to the red edge excitation shift (REES), whereas the additional fluorescence peak is likely associated with charge delocalization along the fiber backbone. Furthermore, the spherulitic amyloid plaque-like superstructures formed from the respective proteins were imaged label-free with confocal fluorescence, multiphoton excitation fluorescence (MPEF), and second-harmonic generation (SHG) microscopy. The latter two techniques in particular yield images with a high contrast between the amyloid fiber regions and the core of amorphously structured protein. Strong multiphoton absorption (MPA) for the amyloid fibers is a likely contributor to the observed contrast in the MPEF images. The crystalline fibrillar region provides even higher contrast in the SHG images, due to the inherently ordered non-centrosymmetric structure of the fibers together with their non-isotropic arrangement. Finally, we show that MPEF from the insulin spherulites exhibits a spectral dependence on the excitation wavelength. This behavior is consistent with the REES phenomenon, which we hypothesize is the origin of this observation. The presented results suggest that amyloid deposits can be identified and structurally characterized based on their intrinsic optical properties, which is important for probe-less and label-free identification and characterization of amyloid fibers in vitro and in complex biological samples. A. 82(12), 4245-4249 (1985). 8. L. C. Serpell, "Alzheimer's amyloid fibrils: structure and assembly," Biochim. Biophys. Acta 1502(1), 16-30 (2000

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Spherulites in Human Brain Tissue are Composed of Beta Sheets of Amyloid and Resemble Senile Plaques

Cited by 16 publications

References 13 publications

The route to protein aggregate superstructures: Particulates and amyloid‐like spherulites

The route to protein aggregate superstructures: Particulates and amyloid‐like spherulites

Ethanol Controls the Self-Assembly and Mesoscopic Properties of Human Insulin Amyloid Spherulites

Label-free imaging of amyloids using their intrinsic linear and nonlinear optical properties

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