Human neuropeptide substance P self-assembles into semi-flexible nanotubes that can be manipulated for nanotechnology

Dharmadana, Durga; Adamčík, Jozef; Ryan, Timothy M.; Danso, Samuel Appiah; Chong, Christopher J.H; Conn, Charlotte E.; Reynolds, Nicholas P.; Mezzenga, Raffaele; Valéry, Céline

doi:10.1039/d0nr05622g

Cited by 10 publications

(11 citation statements)

References 30 publications

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“…For reasons yet unknown, it seems that RNYIAQVD appears to reach a maximum ThT value and then begin to drop, this can be seen at both concentrations but is most obvious at the higher concentration. This could be due to a reversible self-assembly as seen in other functional amyloids 39 , 41 , 43 , 44 , or to self-quenching of the amyloid bound aromatic ThT molecules, or simply to a reduction of exposed ThT-binding sites as larger aggregates with a lower surface area to volume ratio come to dominate the solution.…”

Section: Resultsmentioning

confidence: 99%

Neurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19

et al. 2022

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COVID-19 is primarily known as a respiratory disease caused by SARS-CoV-2. However, neurological symptoms such as memory loss, sensory confusion, severe headaches, and even stroke are reported in up to 30% of cases and can persist even after the infection is over (long COVID). These neurological symptoms are thought to be produced by the virus infecting the central nervous system, however we don’t understand the molecular mechanisms triggering them. The neurological effects of COVID-19 share similarities to neurodegenerative diseases in which the presence of cytotoxic aggregated amyloid protein or peptides is a common feature. Following the hypothesis that some neurological symptoms of COVID-19 may also follow an amyloid etiology we identified two peptides from the SARS-CoV-2 proteome that self-assemble into amyloid assemblies. Furthermore, these amyloids were shown to be highly toxic to neuronal cells. We suggest that cytotoxic aggregates of SARS-CoV-2 proteins may trigger neurological symptoms in COVID-19.

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Section: Resultsmentioning

confidence: 99%

Neurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19

et al. 2022

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“…They have been categorized into three main families: (i) the neurotrophin family, including NGF, BDNF, neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4); (ii) the glial cell line-derived neurotrophic factor (GNDF) family, e.g., GDNF, neurturin (NRTN), artemin (ARTN), and persephin (PSPN); and (iii) the neuropoietic cytokines, e.g., ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), and cardiotrophin (CT-1). Other proteins, such as fibroblast growth factor-1 and -2 (FGF-1 and FGF-2) and platelet-derived growth factor (PDGF), as well as polypeptides, including pituitary adenylate cyclaseactivating peptide (PACAP), insulin-like growth factor 1 (IGF-1), human neuropeptide substance P, macrophage colony-stimulating factor (M-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF), can also play a role as NTFs [47][48][49][50][51][52][53][54][55][56][57][58].…”

Section: Biomolecule Delivery In Neuroregeneration Strategiesmentioning

confidence: 99%

“…An encapsulated cell biodelivery (ECB) device has been demonstrated to be an efficient method to improve NGF levels in AD patients [89]. Other promising approaches have comprised electrode coating materials [82] as well as carrier systems such as hydrogels [83,84], microspheres [85], nanotubes [47], mesoporous silica supraparticles [86], or nanoparticles [87,88].…”

Section: Carrier-mediated Delivery Employing Different Nanoscale Mate...mentioning

confidence: 99%

Self-Assembled Nanoscale Materials for Neuronal Regeneration: A Focus on BDNF Protein and Nucleic Acid Biotherapeutic Delivery

Rakotoarisoa

Angelov

et al. 2022

Nanomaterials

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Enabling challenging applications of nanomedicine and precision medicine in the treatment of neurodegenerative disorders requires deeper investigations of nanocarrier-mediated biomolecular delivery for neuronal targeting and recovery. The successful use of macromolecular biotherapeutics (recombinant growth factors, antibodies, enzymes, synthetic peptides, cell-penetrating peptide–drug conjugates, and RNAi sequences) in clinical developments for neuronal regeneration should benefit from the recent strategies for enhancement of their bioavailability. We highlight the advances in the development of nanoscale materials for drug delivery in neurodegenerative disorders. The emphasis is placed on nanoformulations for the delivery of brain-derived neurotrophic factor (BDNF) using different types of lipidic nanocarriers (liposomes, liquid crystalline or solid lipid nanoparticles) and polymer-based scaffolds, nanofibers and hydrogels. Self-assembled soft-matter nanoscale materials show favorable neuroprotective characteristics, safety, and efficacy profiles in drug delivery to the central and peripheral nervous systems. The advances summarized here indicate that neuroprotective biomolecule-loaded nanoparticles and injectable hydrogels can improve neuronal survival and reduce tissue injury. Certain recently reported neuronal dysfunctions in long-COVID-19 survivors represent early manifestations of neurodegenerative pathologies. Therefore, BDNF delivery systems may also help in prospective studies on recovery from long-term COVID-19 neurological complications and be considered as promising systems for personalized treatment of neuronal dysfunctions and prevention or retarding of neurodegenerative disorders.

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“…For reasons yet unknown, it seems that RNYIAQVD appears to reach a maximum ThT value and then begin to drop, this can be seen at both concentrations but is most obvious at the higher concentration. This could be due to a reversible selfassembly as seen in other functional amyloids, 46,[49][50][51] or to self-quenching of the amyloid bound aromatic ThT molecules, or simply to a reduction of exposed ThT-binding sites as larger aggregates with a lower surface area to volume ratio come to dominate the solution.…”

Section: Assembly Kinetics and Cytotoxicitymentioning

confidence: 99%

Neurotoxic Amyloidogenic Peptides in the Proteome of SARS-COV2: Potential Implications for Neurological Symptoms in COVID-19

Charnley

Islam

Bindra

et al. 2022

Preprint

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COVID-19 is primarily known as a respiratory disease caused by the virus SARS-CoV-2. However, neurological symptoms such as memory loss, sensory confusion, cognitive and psychiatric issues, severe headaches, and even stroke are reported in as many as 30% of cases and can persist even after the infection is over (so-called ‘long COVID’). These neurological symptoms are thought to be caused by brain inflammation, caused by the virus infecting the central nervous system of COVID-19 patients, however we still don’t understand the molecular mechanisms that trigger these symptoms. The neurological effects of COVID-19 share many similarities to neurodegenerative diseases such as Alzheimer’s and Parkinson’s in which the presence of cytotoxic protein-based amyloid aggregates is a common etiological feature. Following the hypothesis that some neurological symptoms of COVID-19 may also follow an amyloid etiology we performed a bioinformatic scan of the SARS-CoV-2 proteome, detecting peptide fragments that were predicted to be highly amyloidogenic. We selected two of these peptides from the open reading frame 6 (ORF6) and open reading frame 10 (ORF10) proteins. The amyloidogenic virus-derived proteins studied in this work did not include spike (S) protein or any other proteins that have been modified to function as antigens in any current vaccines. We discovered that these ORF protein fragments rapidly self-assemble into amyloid aggregates. Furthermore, these amyloid assemblies were shown to be highly toxic to a neuronal cell line. We introduce and support the idea that cytotoxic amyloid aggregates of SARS-CoV-2 proteins are causing some of the neurological symptoms commonly found in COVID-19 and contributing to long COVID.

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Human neuropeptide substance P self-assembles into semi-flexible nanotubes that can be manipulated for nanotechnology

Abstract: Substance P neuropeptide is here reported to self-assemble into well-defined semi-flexible nanotubes. Using a blend of synchrotron small angle X-ray scattering, atomic force microscopy and other biophysical techniques, the natural...

Cited by 10 publications

References 30 publications

Neurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19

Neurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19

Self-Assembled Nanoscale Materials for Neuronal Regeneration: A Focus on BDNF Protein and Nucleic Acid Biotherapeutic Delivery

Neurotoxic Amyloidogenic Peptides in the Proteome of SARS-COV2: Potential Implications for Neurological Symptoms in COVID-19

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