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1.
Chem Commun (Camb) ; 60(69): 9266-9269, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39129415

RESUMEN

A perforated silica layer with structural correlation is engineered using sol-gel chemistry, applied to large-scale flat and curved surfaces. The anion(s) used in the preparation give tailored spatial correlation, and control over perforation size and density. Surface structuration is rapidly and reproducibly created using water and salts as inexpensive and ecofriendly reagents.

2.
Methods ; 230: 59-67, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39047926

RESUMEN

Most bacterial, plant and fungal cells possess at their surface a protective layer called the cell wall, conferring strength, plasticity and rigidity to withstand the osmotic pressure. This molecular barrier is crucial for pathogenic microorganisms, as it protects the cell from the local environment and often constitutes the first structural component encountered in the host-pathogen interaction. In pathogenic molds and yeasts, the cell wall constitutes the main target for the development of clinically-relevant antifungal drugs. In the past decade, solid-state NMR has emerged as a powerful analytical technique to investigate the molecular organization of microbial cell walls in the context of intact cells. 13C NMR chemical shift is an exquisite source of information to identify the polysaccharides present in the cell wall, and two-dimensional 13C-13C correlation experiments provide an efficient tool to rapidly access the polysaccharide composition in whole cells. Here we investigate the use of the adiabatic DREAM (for dipolar recoupling enhancement through amplitude modulation) recoupling scheme to improve solid-state NMR analysis of polysaccharides in intact cells. We demonstrate the advantages of two-dimensional 13C-13C experiments using the DREAM recoupling scheme. We report the spectral editing of polysaccharide signals by varying the radio-frequency carrier position. We provide practical considerations for the implementation of DREAM experiments to characterize polysaccharides in whole cells. We demonstrate the approach on intact fungal cells of Neurospora crassa and Aspergillus fumigatus, a model and a pathogenic filamentous fungus, respectively. The approach could be envisioned to efficiently reduce the spectral crowding of more complex cell surfaces, such as cell wall and peptidoglycan in bacteria.


Asunto(s)
Pared Celular , Polisacáridos , Pared Celular/química , Pared Celular/metabolismo , Polisacáridos/química , Espectroscopía de Resonancia Magnética/métodos , Neurospora crassa , Isótopos de Carbono/química , Aspergillus fumigatus
3.
Biomol NMR Assign ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38907837

RESUMEN

Signalosomes are high-order protein machineries involved in complex mechanisms controlling regulated immune defense and cell death execution. The immune response is initiated by the recognition of exogeneous or endogenous signals, triggering the signalosome assembly process. The final step of signalosome fate often involves membrane-targeting and activation of pore-forming execution domains, leading to membrane disruption and ultimately cell death. Such cell death-inducing domains have been thoroughly characterized in plants, mammals and fungi, notably for the fungal cell death execution protein domain HeLo. However, little is known on the mechanisms of signalosome-based immune response in bacteria, and the conformation of cell death executors in bacterial signalosomes is still poorly characterized. We recently uncovered the existence of NLR signalosomes in various multicellular bacteria and used genome mining approaches to identify putative cell death executors in Streptomyces olivochromogenes. These proteins contain a C-terminal amyloid domain involved in signal transmission and a N-terminal domain, termed BELL for Bacteria analogous to fungal HeLL (HeLo-like), presumably responsible for membrane-targeting, pore-forming and cell death execution. In the present study, we report the high yield expression of S. olivochromogenes BELL2 and its characterization by solution NMR spectroscopy. BELL is folded in solution and we report backbone and sidechain assignments. We identified five α-helical secondary structure elements and a folded core much smaller than its fungal homolog HeLo. This study constitutes the first step toward the NMR investigation of the full-length protein assembly and its membrane targeting.

4.
Nucleic Acids Res ; 52(8): 4124-4136, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38554107

RESUMEN

Pharmacological modulation of RNA splicing by small molecules is an emerging facet of drug discovery. In this context, the SMN2 splicing modifier SMN-C5 was used as a prototype to understand the mode of action of small molecule splicing modifiers and propose the concept of 5'-splice site bulge repair. In this study, we combined in vitro binding assays and structure determination by NMR spectroscopy to identify the binding modes of four other small molecule splicing modifiers that switch the splicing of either the SMN2 or the HTT gene. Here, we determined the solution structures of risdiplam, branaplam, SMN-CX and SMN-CY bound to the intermolecular RNA helix epitope containing an unpaired adenine within the G-2A-1G+1U+2 motif of the 5'-splice site. Despite notable differences in their scaffolds, risdiplam, SMN-CX, SMN-CY and branaplam contact the RNA epitope similarly to SMN-C5, suggesting that the 5'-splice site bulge repair mechanism can be generalised. These findings not only deepen our understanding of the chemical diversity of splicing modifiers that target A-1 bulged 5'-splice sites, but also identify common pharmacophores required for modulating 5'-splice site selection with small molecules.


Asunto(s)
Diseño de Fármacos , Sitios de Empalme de ARN , Empalme del ARN , Humanos , Compuestos Azo , Modelos Moleculares , Conformación de Ácido Nucleico , Pirimidinas , Empalme del ARN/efectos de los fármacos , Proteína 2 para la Supervivencia de la Neurona Motora/genética , Proteína 2 para la Supervivencia de la Neurona Motora/metabolismo
5.
Angew Chem Int Ed Engl ; 62(48): e202311639, 2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-37804233

RESUMEN

We prepared a series of water-soluble aromatic oligoamide sequences all composed of a segment prone to form a single helix and a segment prone to dimerize into a double helix. These sequences exclusively assemble as antiparallel duplexes. The modification of the duplex inner rim by varying the nature of the substituents borne by the aromatic monomers allowed us to identify sequences that can hybridize by combining two chemically different strands, with high affinity and complete selectivity in water. X-ray crystallography confirmed the expected antiparallel configuration of the duplexes whereas NMR spectroscopy and mass spectrometry allowed us to assess precisely the extent of the hybridization. The hybridization kinetics of the aromatic strands was shown to depend on both the nature of the substituents responsible for strand complementarity and the length of the aromatic strand. These results highlight the great potential of aromatic hetero-duplex as a tool to construct non-symmetrical dynamic supramolecular assemblies.

6.
Commun Biol ; 6(1): 1075, 2023 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-37865695

RESUMEN

Hfq is a pleitropic actor that serves as stress response and virulence factor in the bacterial cell. To execute its multiple functions, Hfq assembles into symmetric torus-shaped hexamers. Extending outward from the hexameric core, Hfq presents a C-terminal region, described as intrinsically disordered in solution. Many aspects of the role and the structure of this region remain unclear. For instance, in its truncated form it can promote amyloid-like filament assembly. Here, we show that a minimal 11-residue motif at the C-terminal end of Hfq assembles into filaments with amyloid characteristics. Our data suggest that the full-length Hfq in its filamentous state contains a similar molecular fingerprint than that of the short ß-strand peptide, and that the Sm-core structure is not affected by filament formation. Hfq proteins might thus co-exist in two forms in vivo, either as isolated, soluble hexamers or as self-assembled hexamers through amyloid-reminiscent interactions, modulating Hfq cellular functions.


Asunto(s)
Proteínas de Escherichia coli , Proteínas de Escherichia coli/metabolismo , Escherichia coli/metabolismo , Péptidos beta-Amiloides/metabolismo , Unión Proteica , Proteína de Factor 1 del Huésped/genética , Proteína de Factor 1 del Huésped/metabolismo
7.
Front Mol Biosci ; 10: 1148302, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37065450

RESUMEN

Aberrant aggregation of the transactive response DNA-binding protein (TDP-43) is associated with several lethal neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal dementia. Cytoplasmic neuronal inclusions of TDP-43 are enriched in various fragments of the low-complexity C-terminal domain and are associated with different neurotoxicity. Here we dissect the structural basis of TDP-43 polymorphism using magic-angle spinning solid-state NMR spectroscopy in combination with electron microscopy and Fourier-transform infrared spectroscopy. We demonstrate that various low-complexity C-terminal fragments, namely TDP-13 (TDP-43300-414), TDP-11 (TDP-43300-399), and TDP-10 (TDP-43314-414), adopt distinct polymorphic structures in their amyloid fibrillar state. Our work demonstrates that the removal of less than 10% of the low-complexity sequence at N- and C-termini generates amyloid fibrils with comparable macroscopic features but different local structural arrangement. It highlights that the assembly mechanism of TDP-43, in addition to the aggregation of the hydrophobic region, is also driven by complex interactions involving low-complexity aggregation-prone segments that are a potential source of structural polymorphism.

8.
Anal Chem ; 95(7): 3596-3605, 2023 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-36749686

RESUMEN

Understanding the membrane dynamics of complex systems is essential to follow their function. As molecules in membranes can be in a rigid or mobile state depending on external (temperature, pressure) or internal (pH, domains, etc.) conditions, we propose an in-depth examination of NMR methods to filter highly mobile molecular parts from others that are in more restricted environments. We have thus developed a quantitative magic-angle spinning (MAS) 13C NMR approach coupled with cross-polarization (CP) and/or Insensitive Nuclei Enhanced by Polarization Transfer (INEPT) on rigid and fluid unlabeled model membranes. We demonstrate that INEPT can detect only very mobile lipid headgroups in gel (solid-ordered) phases; the remaining rigid parts are only detected with CP. A direct correlation is established between the normalized line intensity as obtained by CP and the C-H (C-D) order parameters measured by wide-line 2H NMR or extracted from molecular dynamics: ICP/IDPeq ≈ 5|SCH|, indicating that when the order is greater than 0.2-0.3 (maximum value of 0.5 for chain CH2), only rigid parts can be filtered and detected using CP techniques. In very fluid (liquid-disordered) membranes, where there are many more active motions, both INEPT and CP detect resonances, with, however, a clear propensity of each technique to detect mobile and restricted molecular parts, respectively. Interestingly, the 13C NMR chemical shift of lipid hydrocarbon chains can be used to monitor order-disorder phase transitions and calculate the fraction of chain defects (rotamers) and the part of the transition enthalpy due to bond rotations (6-7 kJ·mol-1 for dimyristolphosphatidylcholine, DMPC). Cholesterol-containing membranes (liquid-ordered phases) can be dynamically contrasted as the rigid-body sterol is mainly detected by the CP technique, with a contact time of 1 ms, and the phospholipid by INEPT. Our work opens up a straightforward, robust, and cost-effective route for the determination of membrane dynamics by taking advantage of well-resolved conventional 13C NMR experiments without the need of isotopic labeling.

9.
Angew Chem Int Ed Engl ; 62(19): e202219314, 2023 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-36738230

RESUMEN

Aromatic side chains are important reporters of the plasticity of proteins, and often form important contacts in protein-protein interactions. We studied aromatic residues in the two structurally homologous cross-ß amyloid fibrils HET-s, and HELLF by employing a specific isotope-labeling approach and magic-angle-spinning NMR. The dynamic behavior of the aromatic residues Phe and Tyr indicates that the hydrophobic amyloid core is rigid, without any sign of "breathing motions" over hundreds of milliseconds at least. Aromatic residues exposed at the fibril surface have a rigid ring axis but undergo ring flips on a variety of time scales from nanoseconds to microseconds. Our approach provides direct insight into hydrophobic-core motions, enabling a better evaluation of the conformational heterogeneity generated from an NMR structural ensemble of such amyloid cross-ß architecture.


Asunto(s)
Péptidos beta-Amiloides , Amiloide , Resonancia Magnética Nuclear Biomolecular/métodos , Amiloide/química , Espectroscopía de Resonancia Magnética , Conformación Proteica , Péptidos beta-Amiloides/metabolismo
10.
Chemistry ; 29(12): e202203210, 2023 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-36639240

RESUMEN

In switchable molecular recognition, 1 O2 stimulus responsive receptors offer a unique structural change that is rarely exploited. The employed [4+2] reaction between 1 O2 and anthracene derivatives is quantitative, reversible and easily implemented. To evaluate the full potential of this new stimulus, a non-macrocyclic anthracene-based host was designed for the modular binding of cations. The structural investigation showed that 1 O2 controlled the atropisomerism in an on/off fashion within the pair of hosts. The binding studies revealed higher association constants for the endoperoxide receptor compared to the parent anthracene, due to a more favoured preorganization of the recognition site. The fatigue of the 1 O2 switchable hosts and their complexes was monitored over five cycles of cycloaddition/cycloreversion.

11.
Proc Natl Acad Sci U S A ; 120(6): e2212003120, 2023 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-36719915

RESUMEN

While establishing an invasive infection, the dormant conidia of Aspergillus fumigatus transit through swollen and germinating stages, to form hyphae. During this morphotype transition, the conidial cell wall undergoes dynamic remodeling, which poses challenges to the host immune system and antifungal drugs. However, such cell wall reorganization during conidial germination has not been studied so far. Here, we explored the molecular rearrangement of Aspergillus fumigatus cell wall polysaccharides during different stages of germination. We took advantage of magic-angle spinning NMR to investigate the cell wall polysaccharides, without employing any destructive method for sample preparation. The breaking of dormancy was associated with a significant change in the molar ratio between the major polysaccharides ß-1,3-glucan and α-1,3-glucan, while chitin remained equally abundant. The use of various polarization transfers allowed the detection of rigid and mobile polysaccharides; the appearance of mobile galactosaminogalactan was a molecular hallmark of germinating conidia. We also report for the first time highly abundant triglyceride lipids in the mobile matrix of conidial cell walls. Water to polysaccharides polarization transfers revealed an increased surface exposure of glucans during germination, while chitin remained embedded deeper in the cell wall, suggesting a molecular compensation mechanism to keep the cell wall rigidity. We complement the NMR analysis with confocal and atomic force microscopies to explore the role of melanin and RodA hydrophobin on the dormant conidial surface. Exemplified here using Aspergillus fumigatus as a model, our approach provides a powerful tool to decipher the molecular remodeling of fungal cell walls during their morphotype switching.


Asunto(s)
Aspergillus fumigatus , Proteínas Fúngicas , Aspergillus fumigatus/metabolismo , Esporas Fúngicas/metabolismo , Proteínas Fúngicas/metabolismo , Polisacáridos/metabolismo , Quitina/metabolismo , Glucanos/metabolismo , Pared Celular/metabolismo
12.
Biochim Biophys Acta Biomembr ; 1865(2): 184097, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36442647

RESUMEN

Since the first membrane models in the 1970s, the concept of biological membranes has evolved considerably. The membrane is now seen as a very complex mixture whose dynamic behavior is even more complex. Solid-state NMR is well suited for such studies as it can probe the movements of the membrane from picoseconds to seconds. Two NMR observables can be used: motionally averaged spectra and relaxation times. They bring information on order parameters, phase transitions, correlation times, activation energies and membrane elasticity. Spectra are used to determine the nature of the membrane phase. The order parameters can be measured directly from spectra that are dominated by quadrupolar, dipolar and chemical shielding magnetic interactions and allow describing the lipid membrane as being very rigid at the glycerol and chain level and very fluid at its center and surface. Correlation times and activation energies can be measured for intramolecular motions (pico to nanoseconds), molecular motions (nano to 100 ns) and collective modes of membrane deformation (microseconds). Sterols modulate membrane phases, order parameters, correlation times and membrane elasticity. In general terms, sterols tend to act to reduce the impact of environmental changes on molecular order and dynamics. They can be described as regulators of membrane dynamics by keeping them in a state of dynamics that changes very little when the temperature or other factors change. The presence of such large-scale membrane dynamics is proposed as a means of adapting to evolutionary constraints.


Asunto(s)
Esteroles , Espectroscopía de Resonancia Magnética , Elasticidad , Membranas , Movimiento (Física)
13.
Commun Biol ; 5(1): 1202, 2022 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-36352173

RESUMEN

Structural investigations of amyloid fibrils often rely on heterologous bacterial overexpression of the protein of interest. Due to their inherent hydrophobicity and tendency to aggregate as inclusion bodies, many amyloid proteins are challenging to express in bacterial systems. Cell-free protein expression is a promising alternative to classical bacterial expression to produce hydrophobic proteins and introduce NMR-active isotopes that can improve and speed up the NMR analysis. Here we implement the cell-free synthesis of the functional amyloid prion HET-s(218-289). We present an interesting case where HET-s(218-289) directly assembles into infectious fibril in the cell-free expression mixture without the requirement of denaturation procedures and purification. By introducing tailored 13C and 15N isotopes or CF3 and 13CH2F labels at strategic amino-acid positions, we demonstrate that cell-free synthesized amyloid fibrils are readily amenable to high-resolution magic-angle spinning NMR at sub-milligram quantity.


Asunto(s)
Amiloide , Priones , Amiloide/química , Espectroscopía de Resonancia Magnética/métodos , Proteínas Amiloidogénicas , Imagen por Resonancia Magnética
14.
Chemistry ; 28(72): e202202695, 2022 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-36316221

RESUMEN

Chiral trifluoromethyl alcohol groups were introduced at the hindered ortho positions of 9,10-diphenylanthracenes to investigate their effects on the physical properties and reactivity towards oxidative dearomatization. In such compact structures, the position in different quadrants and the preferred orientation of the -CH(OH)CF3 groups were determined by the relative and absolute configurations of each stereoisomer, respectively. As a consequence, the stereochemistry governs the organization of the H-bonded molecules in single crystals (homochiral dimers vs ribbon), whereas in chlorinated solvents, they all behave as discrete compounds. Concerning their reactivity, the stereospecific dearomative oxidation of these molecules leads to 9,10-bis-spiro-isobenzofuran-anthracenes, when using organic single-electron transfer oxidants. The chiroptical properties of the alcohols and the corresponding dearomatized products were compared and showed an important modulation of the intensity.

15.
J Am Chem Soc ; 144(35): 15988-15998, 2022 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-35998571

RESUMEN

Amphipathic water-soluble helices formed from synthetic peptides or foldamers are promising building blocks for the creation of self-assembled architectures with non-natural shapes and functions. While rationally designed artificial quaternary structures such as helix bundles have been shown to contain preformed cavities suitable for guest binding, there are no examples of adaptive binding of guest molecules by such assemblies in aqueous conditions. We have previously reported a foldamer 6-helix bundle that contains an internal nonpolar cavity able to bind primary alcohols as guest molecules. Here, we show that this 6-helix bundle can also interact with larger, more complex guests such as n-alkyl glycosides. X-ray diffraction analysis of co-crystals using a diverse set of guests together with solution and gas-phase studies reveals an adaptive binding mode whereby the apo form of the 6-helix bundle undergoes substantial conformational change to accommodate the hydrocarbon chain in a manner reminiscent of glycolipid transfer proteins in which the cavity forms upon lipid uptake. The dynamic nature of the self-assembling and molecular recognition processes reported here marks a step forward in the design of functional proteomimetic molecular assemblies.


Asunto(s)
Glucolípidos , Agua , Glicósidos , Péptidos/química , Proteínas
16.
Nucleic Acids Res ; 50(12): 7134-7146, 2022 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-35736226

RESUMEN

The Caenorhabditis elegans model has greatly contributed to the understanding of the role of G-quadruplexes in genomic instability. The GGCTTA repeats of the C. elegans telomeres resemble the GGGTTA repeats of the human telomeres. However, the comparison of telomeric sequences (Homo sapiens, Tetrahymena, Oxytricha, Bombyx mori and Giardia) revealed that small changes in these repeats can drastically change the topology of the folded G-quadruplex. In the present work we determined the structure adopted by the C. elegans telomeric sequence d[GG(CTTAGG)3]. The investigated C. elegans telomeric sequence is shown to fold into an intramolecular two G-tetrads basket type G-quadruplex structure that includes a C-T base pair in the diagonal loop. This work sheds light on the telomeric structure of the widely used C. elegans animal model.


Asunto(s)
Caenorhabditis elegans , G-Cuádruplex , Telómero , Animales , Humanos , Emparejamiento Base , Caenorhabditis elegans/genética , Telómero/química
17.
Front Mol Neurosci ; 14: 670513, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34276304

RESUMEN

Infectious proteins or prions are a remarkable class of pathogens, where pathogenicity and infectious state correspond to conformational transition of a protein fold. The conformational change translates into the formation by the protein of insoluble amyloid aggregates, associated in humans with various neurodegenerative disorders and systemic protein-deposition diseases. The prion principle, however, is not limited to pathogenicity. While pathological amyloids (and prions) emerge from protein misfolding, a class of functional amyloids has been defined, consisting of amyloid-forming domains under natural selection and with diverse biological roles. Although of great importance, prion amyloid structures remain challenging for conventional structural biology techniques. Solid-state nuclear magnetic resonance (SSNMR) has been preferentially used to investigate these insoluble, morphologically heterogeneous aggregates with poor crystallinity. SSNMR methods have yielded a wealth of knowledge regarding the fundamentals of prion biology and have helped to solve the structures of several prion and prion-like fibrils. Here, we will review pathological and functional amyloid structures and will discuss some of the obtained structural models. We will finish the review with a perspective on integrative approaches combining solid-state NMR, electron paramagnetic resonance and cryo-electron microscopy, which can complement and extend our toolkit to structurally explore various facets of prion biology.

18.
J Colloid Interface Sci ; 594: 857-863, 2021 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-33794407

RESUMEN

Supramolecular chemistry has garnered important interest in recent years toward improving therapeutic efficacy via drug delivery approaches. Although self-assemblies have been deeply investigated, the design of novel drugs leveraging supramolecular chemistry is less known. In this contribution, we show that a Low Molecular Weight Gel (LMWG) can elicit cancer cell apoptosis. This biological effect results from the unique supramolecular properties of a bolaamphiphile-based gelator, which allow for strong interaction with the lipid membrane. This novel supramolecular-drug paradigm opens up new possibilities for therapeutic applications targeting membrane lipids.


Asunto(s)
Sistemas de Liberación de Medicamentos , Furanos , Geles , Piridonas
19.
Chemistry ; 27(43): 11205-11215, 2021 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-33905165

RESUMEN

The alkylation of some secondary amide functions with a dimethoxybenzyl (DMB) group in oligomers of 8-amino-2-quinolinecarboxylic acid destabilizes the otherwise favored helical conformations, and allows for cyclization to take place. A cyclic hexamer and a cyclic heptamer were produced in this manner. After DMB removal, X-ray crystallography and NMR show that the macrocycles adopt strained conformations that would be improbable in noncyclic species. The high helix folding propensity of the main chain is partly expressed in these conformations, but it remains frustrated by macrocyclization. Despite being homomeric, the macrocycles possess inequivalent monomer units. Experimental and computational studies highlight specific fluxional pathways within these structures. Extensive simulated annealing molecular dynamics allow for the prediction of the conformations for larger macrocycles with up to sixteen monomers.


Asunto(s)
Amidas , Cristalografía por Rayos X , Ciclización , Modelos Moleculares , Conformación Molecular
20.
Sci Adv ; 6(40)2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33008896

RESUMEN

The conformational strain diversity characterizing α-synuclein (α-syn) amyloid fibrils is thought to determine the different clinical presentations of neurodegenerative diseases underpinned by a synucleinopathy. Experimentally, various α-syn fibril polymorphs have been obtained from distinct fibrillization conditions by altering the medium constituents and were selected by amyloid monitoring using the probe thioflavin T (ThT). We report that, concurrent with classical ThT-positive products, fibrillization in saline also gives rise to polymorphs invisible to ThT (τ-). The generation of τ- fibril polymorphs is stochastic and can skew the apparent fibrillization kinetics revealed by ThT. Their emergence has thus been ignored so far or mistaken for fibrillization inhibitions/failures. They present a yet undescribed atomic organization and show an exacerbated propensity toward self-replication in cortical neurons, and in living mice, their injection into the substantia nigra pars compacta triggers a synucleinopathy that spreads toward the dorsal striatum, the nucleus accumbens, and the insular cortex.


Asunto(s)
Sinucleinopatías , alfa-Sinucleína , Amiloide , Animales , Benzotiazoles , Ratones , Neuronas
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