Probing protein aggregation through spectroscopic insights and multimodal approaches: A comprehensive review for counteracting neurodegenerative disorders

Heliyon, Journal Year: 2024, Volume and Issue: 10(7), P. e27949 - e27949

Published: March 18, 2024

Aberrant accumulation of protein misfolding can cause aggregation and fibrillation is one the primary characteristic features neurodegenerative diseases. Because they are disordered, misfolded, aggregated proteins pose a significant setback in drug designing. The structural study intermediate steps these kinds will allow us to determine conformational changes as well probable pathways encompassing various disorders. analysis aggregates involved diseases relies on diverse toolkit biophysical techniques, both morphological non-morphological methods. Additionally, Thioflavin T (ThT) assays Circular Dichroism (CD) spectroscopy facilitate investigations into kinetics secondary structure alterations. collective application techniques empowers researchers comprehensively unravel intricate nature associated with neurodegeneration. Furthermore, topics covered this review have summed up handful well-established used for aggregation. This multifaceted approach advances our fundamental understanding underlying mechanisms driving informs potential therapeutic strategies.

Language: Английский

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Exploring Tau Fibril-Disaggregating and Antioxidating Molecules Binding to Membrane-Bound Amyloid Oligomers Using Machine Learning-Enhanced Docking and Molecular Dynamics

Molecules, Journal Year: 2024, Volume and Issue: 29(12), P. 2818 - 2818

Published: June 13, 2024

Intracellular tau fibrils are sources of neurotoxicity and oxidative stress in Alzheimer’s. Current drug discovery efforts have focused on molecules with fibril disaggregation antioxidation functions. However, recent studies suggest that membrane-bound tau-containing oligomers (mTCOs), smaller less ordered than fibrils, neurotoxic the early stage Whether fibril-targeting effective against mTCOs is unknown. The binding epigallocatechin-3-gallate (EGCG), CNS-11, BHT-CNS-11 to silico experimental was investigated using machine learning-enhanced docking molecular dynamics simulations. EGCG CNS-11 functions, while proposed has potential functions like EGCG. Our results three studied may also bind mTCOs. predicted probability increases protein aggregate size. In contrast, dimeric higher tetrameric for homo but not hetero tau–amylin oligomers. support idea anionic lipids promote We conclude fibril-disaggregating antioxidating mTCOs, be useful targets Alzheimer’s design.

Language: Английский

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Quantitative systems pharmacology‐based exploration of relevant anti‐amyloid therapy challenges in clinical practice

Alzheimer s & Dementia Translational Research & Clinical Interventions, Journal Year: 2024, Volume and Issue: 10(2)

Published: April 1, 2024

Addressing practical challenges in clinical practice after the recent approvals of amyloid antibodies Alzheimer's disease (AD) will benefit more patients. However, generating these answers using trials or real-world evidence is not practical, nor feasible.

Language: Английский

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Targeting Intrinsically Disordered Proteins (IDPs) in Drug Discovery

Published: Nov. 29, 2024

"Revolutionizing Drug Delivery Through Computational Design: Nanotechnology and Personalized Therapeutics" explores the transformative potential of computational methodologies in advancing drug delivery systems. This chapter delves into intersection nanotechnology personalized medicine, highlighting how design techniques have revolutionized development targeted efficient drug-delivery vehicles. integration advanced algorithms modeling approaches, researchers can optimize formulations, enhance efficiency, tailor treatments to individual patient profiles. Key topics include role artificial intelligence, nanomaterials, real-time monitoring shaping future delivery. Furthermore, emphasizes importance interdisciplinary collaboration driving innovation overcoming challenges this rapidly evolving field. The promise therapeutics improving outcomes is underscored, with a focus on precision medicine approaches. Overall, provides insights current state research outlines directions for harnessing address unmet medical needs.

Language: Английский

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Authentic hSAA related with AA amyloidosis: New method of purification, folding and amyloid polymorphism

Biophysical Chemistry, Journal Year: 2024, Volume and Issue: 313, P. 107293 - 107293

Published: July 10, 2024

Language: Английский

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