Destabilization potential of beta sheet breaker peptides on Abeta fibril structure: an insight from molecular dynamics simulation study

Jani, Vinod; Sonavane, Uddhavesh; Joshi, Rajendra

doi:10.1039/d1ra03609b

Cited by 7 publications

(3 citation statements)

References 88 publications

(132 reference statements)

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“…In another study, the destabilization potential of BSB peptides of varying lengths (5-mer to 10-mer) against preformed Ab 42 protofibril was scrutinized using MD simulations. 20 The 7-mer peptide KKLVFFA showed better destabilization ability against Ab 42 protofibril as compared to other BSB peptides.…”

Section: Introductionmentioning

confidence: 91%

Mechanistic insights into the mitigation of Aβ aggregation and protofibril destabilization by ad-enantiomeric decapeptide rk10

Singh

Kaur

Goyal³

et al. 2022

Phys. Chem. Chem. Phys.

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Section: Introductionmentioning

confidence: 91%

Mechanistic insights into the mitigation of Aβ aggregation and protofibril destabilization by ad-enantiomeric decapeptide rk10

Singh

Kaur

Goyal³

et al. 2022

Phys. Chem. Chem. Phys.

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“…For example, the small molecule (10074-G5) stabilizes the soluble state of Aβ and inhibits nucleation steps in the aggregation process (Heller et al, 2020). Tricyclic pyrone molecules (CP2 and TP3) (Hong et al, 2009), beta sheet breaker peptide (Jani et al, 2021), D-enantiomeric peptide (Rösener et al, 2018) and others (Seidler et al, 2022;Murray et al, 2023), also have been highlighted as therapeutic options to prevent the formation of Aβ fibrils.…”

Section: Modulation Of Protein Aggregation With Small Molecules Pepti...mentioning

confidence: 99%

Phase separation and pathologic transitions of RNP condensates in neurons: implications for amyotrophic lateral sclerosis, frontotemporal dementia and other neurodegenerative disorders

Naskar,

Nayak,

Salaikumaran

et al. 2023

Front. Mol. Neurosci.

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Liquid–liquid phase separation results in the formation of dynamic biomolecular condensates, also known as membrane-less organelles, that allow for the assembly of functional compartments and higher order structures within cells. Multivalent, reversible interactions between RNA-binding proteins (RBPs), including FUS, TDP-43, and hnRNPA1, and/or RNA (e.g., RBP-RBP, RBP-RNA, RNA-RNA), result in the formation of ribonucleoprotein (RNP) condensates, which are critical for RNA processing, mRNA transport, stability, stress granule assembly, and translation. Stress granules, neuronal transport granules, and processing bodies are examples of cytoplasmic RNP condensates, while the nucleolus and Cajal bodies are representative nuclear RNP condensates. In neurons, RNP condensates promote long-range mRNA transport and local translation in the dendrites and axon, and are essential for spatiotemporal regulation of gene expression, axonal integrity and synaptic function. Mutations of RBPs and/or pathologic mislocalization and aggregation of RBPs are hallmarks of several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Alzheimer’s disease. ALS/FTD-linked mutations of RBPs alter the strength and reversibility of multivalent interactions with other RBPs and RNAs, resulting in aberrant phase transitions. These aberrant RNP condensates have detrimental functional consequences on mRNA stability, localization, and translation, and ultimately lead to compromised axonal integrity and synaptic function in disease. Pathogenic protein aggregation is dependent on various factors, and aberrant dynamically arrested RNP condensates may serve as an initial nucleation step for pathologic aggregate formation. Recent studies have focused on identifying mechanisms by which neurons resolve phase transitioned condensates to prevent the formation of pathogenic inclusions/aggregates. The present review focuses on the phase separation of neurodegenerative disease-linked RBPs, physiological functions of RNP condensates, and the pathologic role of aberrant phase transitions in neurodegenerative disease, particularly ALS/FTD. We also examine cellular mechanisms that contribute to the resolution of aberrant condensates in neurons, and potential therapeutic approaches to resolve aberrantly phase transitioned condensates at a molecular level.

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“…In another study, the authors screened several peptides able to induce protofibril destabilization, displaying that the KKLVFFA peptide provided the maximum perturbation in the protofibril structure [ 121 ]. Jamula et al made a step forward towards more efficient Abeta fibril dissolution by building a BSB using iAb5p as a backbone and adding three phenylalanines (iab6) to dock around position 20 in the CHC zone of Abeta, a position known to be crucial for the action of the BSB inhibitor role [ 122 ].…”

Section: Beta-sheet Breaker (Bsb) Peptides As Abeta Aggregation-inhib...mentioning

confidence: 99%

From Small Peptides to Large Proteins against Alzheimer’sDisease

et al. 2022

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Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the elderly. The two cardinal neuropathological hallmarks of AD are the senile plaques, which are extracellular deposits mainly constituted by beta-amyloids, and neurofibrillary tangles formed by abnormally phosphorylated Tau (p-Tau) located in the cytoplasm of neurons. Although the research has made relevant progress in the management of the disease, the treatment is still lacking. Only symptomatic medications exist for the disease, and, in the meantime, laboratories worldwide are investigating disease-modifying treatments for AD. In the present review, results centered on the use of peptides of different sizes involved in AD are presented.

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Destabilization potential of beta sheet breaker peptides on Abeta fibril structure: an insight from molecular dynamics simulation study

Abstract: Destabilzation of Abeta protofibril by Beta Sheet Breaker (BSB) peptides.

Cited by 7 publications

References 88 publications

Mechanistic insights into the mitigation of Aβ aggregation and protofibril destabilization by ad-enantiomeric decapeptide rk10

Mechanistic insights into the mitigation of Aβ aggregation and protofibril destabilization by ad-enantiomeric decapeptide rk10

Phase separation and pathologic transitions of RNP condensates in neurons: implications for amyotrophic lateral sclerosis, frontotemporal dementia and other neurodegenerative disorders

From Small Peptides to Large Proteins against Alzheimer’sDisease

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