Protein structure and dynamics in the era of integrative structural biology DOI Creative Commons
Rita Grandori

Frontiers in Biophysics, Год журнала: 2023, Номер 1

Опубликована: Июль 17, 2023

Proteins carry out their biological activity as dynamic structures and populate in solution or membranes structural distributions with different degrees of heterogeneity. The central challenge biology is to capture protein dynamics under equilibrium kinetic conditions shifting from single, static pictures movies conformational ensembles. Ideally, this task should be pursued both vitro vivo , the influence native environment. last decade has seen a tremendous development biophysical methods for investigation structure dynamics. However, each method specific limitations no single approach offers such complex level description. Nonetheless, combination experimental computational, complementary opening promising new avenues. Also ambition implementing studies on an “omic” scale becoming more realistic. In spite still major limitations, integrative bringing into proteomics, exciting perspectives basic applied sciences.

Язык: Английский

Interplay of Proteostasis Capacity and Protein Aggregation: Implications for Cellular Function and Disease DOI Creative Commons
Mark S. Hipp, F. Ulrich Hartl

Journal of Molecular Biology, Год журнала: 2024, Номер 436(14), С. 168615 - 168615

Опубликована: Май 16, 2024

Eukaryotic cells are equipped with an intricate proteostasis network (PN), comprising nearly 3,000 components dedicated to preserving proteome integrity and sustaining protein homeostasis. This protective system is particularly important under conditions of external intrinsic cell stress, where inherently dynamic proteins may unfold lose functionality. A decline in capacity associated the aging process, resulting a reduced folding efficiency newly synthesized deficit cellular degrade misfolded proteins. critical consequence PN insufficiency accumulation cytotoxic aggregates that underlie various age-related neurodegenerative other pathologies. By interfering specific components, toxic place excessive burden on PN's ability maintain integrity. initiates feed-forward loop, wherein generation aggregated ultimately leads collapse demise.

Язык: Английский

Процитировано

17
Targeting protein kinases for the treatment of Alzheimer's disease: Recent progress and future perspectives DOI
Zhijia Li, Bo Yin,

Shuangqian Zhang

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 261, С. 115817 - 115817

Опубликована: Сен. 14, 2023

Язык: Английский

Процитировано

29
Current Technologies Unraveling the Significance of Post-Translational Modifications (PTMs) as Crucial Players in Neurodegeneration DOI Creative Commons
Saima Zafar,

Shehzadi Irum Fatima,

Matthias Schmitz

и другие.

Biomolecules, Год журнала: 2024, Номер 14(1), С. 118 - 118

Опубликована: Янв. 16, 2024

Neurodegenerative disorders, such as Parkinson’s disease, Alzheimer’s and Huntington’s are identified characterized by the progressive loss of neurons neuronal dysfunction, resulting in cognitive motor impairment. Recent research has shown importance PTMs, phosphorylation, acetylation, methylation, ubiquitination, sumoylation, nitration, truncation, O-GlcNAcylation, hydroxylation, progression neurodegenerative disorders. PTMs can alter protein structure function, affecting stability, localization, interactions, enzymatic activity. Aberrant lead to misfolding aggregation, impaired degradation, clearance, ultimately, dysfunction death. The main objective this review is provide an overview involved neurodegeneration, their underlying mechanisms, methods isolate potential therapeutic targets for these discussed article include tau α-synuclein Huntingtin histone acetylation RNA modifications. Understanding role diseases may new strategies devastating

Язык: Английский

Процитировано

11
Flavonoids as Potential Therapeutics Against Neurodegenerative Disorders: Unlocking the Prospects DOI
Md. Faysal,

Zerrouki Dehbia,

Mehrukh Zehravi

и другие.

Neurochemical Research, Год журнала: 2024, Номер 49(8), С. 1926 - 1944

Опубликована: Июнь 1, 2024

Язык: Английский

Процитировано

8
Controversial Properties of Amyloidogenic Proteins and Peptides: New Data in the COVID Era DOI Creative Commons
Andrei Surguchov, Fatemeh Nouri Emamzadeh,

Mariya Titova

и другие.

Biomedicines, Год журнала: 2023, Номер 11(4), С. 1215 - 1215

Опубликована: Апрель 19, 2023

For a long time, studies of amyloidogenic proteins and peptides (amyloidogenic PPs) have been focused basically on their harmful properties association with diseases. A vast amount research has investigated the structure pathogenic amyloids forming fibrous deposits within or around cells mechanisms detrimental actions. Much less known about physiologic functions beneficial PPs. At same PPs various useful properties. example, they may render neurons resistant to viral infection propagation stimulate autophagy. We discuss here some PPs’ using as examples beta-amyloid (β-amyloid), implicated in pathogenesis Alzheimer’s disease (AD), α-synuclein—one hallmarks Parkinson’s (PD). Recently antiviral antimicrobial attracted attention because COVID-19 pandemic growing threat other bacterial-induced Importantly, several proteins, e.g., spike, nucleocapsid, envelope become after combine action effect endogenous APPs. central area current investigations is study structural PPs, defining properties, identifying triggers that transform physiologically important into vicious substances. These directions are paramount importance during SARS-CoV-2 global health crisis.

Язык: Английский

Процитировано

19
Amyloids, amorphous aggregates and assemblies of peptides – Assessing aggregation DOI
Maja Juković, Ivana Ratkaj, Daniela Kalafatović

и другие.

Biophysical Chemistry, Год журнала: 2024, Номер 308, С. 107202 - 107202

Опубликована: Фев. 15, 2024

Язык: Английский

Процитировано

6
Detection of TurboID fusion proteins by fluorescent streptavidin outcompetes antibody signals and visualises targets not accessible to antibodies DOI Creative Commons
Johanna Odenwald, Bernardo Gabiatti, Silke Braune

и другие.

eLife, Год журнала: 2024, Номер 13

Опубликована: Авг. 29, 2024

Immunofluorescence localises proteins via fluorophore-labelled antibodies. However, some evade detection due to antibody-accessibility issues or because they are naturally low abundant antigen density is reduced by the imaging method. Here, we show that fusion of target protein biotin ligase TurboID and subsequent biotinylation fluorescent streptavidin offers an ‘all in one’ solution these restrictions. For all tested, signal was significantly stronger than antibody signal, markedly improving sensitivity expansion microscopy correlative light electron microscopy. Importantly, within phase-separated regions, such as central channel nuclear pores, nucleolus, RNA granules, were readily detected with streptavidin, while most antibodies failed. When used tandem HA epitope tag, co-probing anti-HA can map created a for trypanosome pore. Lastly, resolves dynamic, temporally, spatially distinct sub-complexes and, specific cases, reveals history dynamic interaction. In conclusion, has major advantages lowly inaccessible addition, provides information on interactions biophysical environment.

Язык: Английский

Процитировано

5
Spectral Fluorescence Pathology of Protein Misfolding Disorders DOI
Anastasiia A. Stepanchuk, Peter K. Stys

ACS Chemical Neuroscience, Год журнала: 2024, Номер 15(5), С. 898 - 908

Опубликована: Фев. 26, 2024

Protein misfolding has been extensively studied in the context of neurodegenerative disorders and systemic amyloidoses. Due to aggregation proteins being highly heterogeneous generating a variety structures, growing body evidence illustrates numerous ways how aggregates contribute progression diseases such as Alzheimer's disease, Parkinson's prion disorders. Different misfolded species same protein, commonly referred strains, appear play significant role shaping disease clinical phenotype progression. The distinct toxicity profiles various underscore their importance. Current diagnostics struggle differentiate among these strains early course. This review explores potential spectral fluorescence approaches illuminate complexities protein pathology discusses applications advanced methods detection characterization By examining spectrally variable probes, current data analysis approaches, important considerations for use techniques, this aims provide an overview progress made field highlights directions future research.

Язык: Английский

Процитировано

4
A Survey on Computational Methods in Drug Discovery for Neurodegenerative Diseases DOI Creative Commons

Caterina Vicidomini,

Francesco Fontanella, Tiziana D’Alessandro

и другие.

Biomolecules, Год журнала: 2024, Номер 14(10), С. 1330 - 1330

Опубликована: Окт. 19, 2024

Currently, the age structure of world population is changing due to declining birth rates and increasing life expectancy. As a result, physicians worldwide have treat an number age-related diseases, which neurological disorders represent significant part. In this context, there urgent need discover new therapeutic approaches counteract effects neurodegeneration on human health, computational science can be pivotal importance for more effective neurodrug discovery. The knowledge molecular receptors other biomolecules involved in pathogenesis facilitates design molecules as potential drugs used fight against diseases high social relevance such dementia, Alzheimer's disease (AD) Parkinson's (PD), cite only few. However, absence comprehensive guidelines regarding strengths weaknesses alternative creates fragmented disconnected field, resulting missed opportunities enhance performance achieve successful applications. This review aims summarize some most innovative strategies based methods development. particular, recent applications state-of-the-art docking artificial intelligence ligand- target-based novel drug were reviewed, highlighting crucial role silico context discovery neurodegenerative diseases.

Язык: Английский

Процитировано

4
Super-resolution microscopy as drug discovery tool DOI Creative Commons

Lauren Toms,

Louis J Fitzpatrick,

Philip Auckland

и другие.

SLAS DISCOVERY, Год журнала: 2025, Номер 31, С. 100209 - 100209

Опубликована: Янв. 15, 2025

At the turn of century a fundamental resolution barrier in fluorescence microscopy known as diffraction limit was broken, giving rise to field super-resolution microscopy. Subsequent nanoscopic investigation with visible light revolutionised our understanding how previously unknown molecular features give emergent behaviour cells. It transpires that devil is these fine details, and essential nanoscale processes were found everywhere researchers chose look. Now, after nearly two decades, has begun address unmet challenges study human disease poised become pivotal tool drug discovery.

Язык: Английский

Процитировано

0