Biochemical approaches to assess the impact of post-translational modifications on pathogenic tau conformations using recombinant protein DOI Creative Commons
Mohammed M. Alhadidy, Nicholas M. Kanaan

Biochemical Society Transactions, Journal Year: 2024, Volume and Issue: 52(1), P. 301 - 318

Published: Feb. 13, 2024

Tau protein is associated with many neurodegenerative disorders known as tauopathies. Aggregates of tau are thought a main contributor to neurodegeneration in these diseases. Increasingly, evidence points earlier, soluble conformations abnormally modified monomers and multimeric toxic forms tau. The biological processes driving from physiological species pathogenic remain poorly understood, but certain avenues currently under investigation including the functional consequences various pathological changes (e.g. mutations, post-translational modifications (PTMs), protein-protein interactions). PTMs can regulate several aspects biology such proteasomal autophagic clearance, solubility, aggregation. Moreover, contribute transition normal conformations. However, our understating how specifically into partly impeded by relative lack structured frameworks assess quantify In this review, we describe set approaches that includes vitro assays determine contribution tau's begin different methods create recombinant proteins carrying specific followed validation status. Then, biochemical biophysical given PTM conformations, aggregation, oligomerization, exposure phosphatase-activating domain, seeding. Together, facilitate advancement understanding relationships between

Language: Английский

Intrinsically Disordered Proteins: An Overview DOI Open Access
Rakesh Trivedi, Hampapathalu Adimurthy Nagarajaram

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(22), P. 14050 - 14050

Published: Nov. 14, 2022

Many proteins and protein segments cannot attain a single stable three-dimensional structure under physiological conditions; instead, they adopt multiple interconverting conformational states. Such intrinsically disordered or are highly abundant across proteomes, involved in various effector functions. This review focuses on different aspects of regions, which form the basis so-called “Disorder–function paradigm” proteins. Additionally, experimental approaches computational tools used for characterizing regions discussed. Finally, role diseases their utility as potential drug targets explored.

Language: Английский

Citations

107
Specific post-translational modifications of soluble tau protein distinguishes Alzheimer’s disease and primary tauopathies DOI Creative Commons
Nathalie Kyalu Ngoie Zola, Clémence Balty, Sébastien Pyr dit Ruys

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: June 22, 2023

Tau protein aggregates in several neurodegenerative disorders, referred to as tauopathies. The tau isoforms observed post mortem human brain is used classify However, distinguishing tauopathies ante remains challenging, potentially due differences between insoluble and soluble body fluids. Here, we demonstrated that differ aggregates, but not extracts. We therefore characterized post-translational modifications of both the aggregated obtained from tissue patients with Alzheimer's disease, cortico-basal degeneration, Pick's frontotemporal lobe degeneration. found specific signatures for each tauopathy its isoforms: including ubiquitination on Lysine 369 degeneration acetylation 311 disease. These findings provide potential targets future development fluid-based biomarker assays able distinguish vivo.

Language: Английский

Citations

43
Inflammatory aspects of Alzheimer’s disease DOI
Pablo Botella Lucena, Michael T. Heneka

Acta Neuropathologica, Journal Year: 2024, Volume and Issue: 148(1)

Published: Aug. 28, 2024

Language: Английский

Citations

26
The effect of Tau K677 lactylation on ferritinophagy and ferroptosis in Alzheimer's disease DOI Creative Commons

Xiaoqiong An,

Jun He,

Peng Xie

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 224, P. 685 - 706

Published: Sept. 21, 2024

Language: Английский

Citations

9
Temperature-Dependent Aggregation of Tau Protein Is Attenuated by Native PLGA Nanoparticles Under in vitro Conditions DOI Creative Commons

Pallabi Sil Paul,

Mallesh Rathnam,

Aria Khalili

et al.

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 1999 - 2019

Published: Feb. 1, 2025

Hyperphosphorylation and aggregation of the microtubule-associated tau protein, which plays a critical role in many neurodegenerative diseases (ie, tauopathies) including Alzheimer's disease (AD), are known to be regulated by variety environmental factors temperature. In this study we evaluated effects FDA-approved poly (D,L-lactide-co-glycolic) acid (PLGA) nanoparticles, can inhibit amyloid-β aggregation/toxicity cellular/animal models AD, on temperature-dependent 0N4R isoforms vitro. We have used biophysical (Thioflavin T kinetics, dynamic light scattering asymmetric-flow field-flow fractionation), structural (fluorescence imaging transmission electron microscopy) biochemical (Filter-trap assay detection soluble protein) approaches, evaluate native PLGA nanoparticles aggregation. Our results show that propensity increases significantly dose-dependent manner with rise temperature from 27°C 40°C, as measured lag time rate. Additionally, 2N4R manner. Native inhibits at all temperatures concentration-dependent manner, possibly interacting aggregation-prone hydrophobic hexapeptide motifs tau. is able trigger disassembly preformed aggregates function 40°C. These results, taken together, suggest not only attenuate but also promote aggregates, increased Given evidence influence pathology, believe may unique potential regulate abnormalities associated AD-related pathology.

Language: Английский

Citations

1
The multiple facets of acetyl-CoA metabolism: Energetics, biosynthesis, regulation, acylation and inborn errors DOI

Youlin Wang,

Hao Yang,

Chloé Geerts

et al.

Molecular Genetics and Metabolism, Journal Year: 2022, Volume and Issue: 138(1), P. 106966 - 106966

Published: Nov. 30, 2022

Language: Английский

Citations

33
Alzheimer's disease: The role of proteins in formation, mechanisms, and new therapeutic approaches DOI

Amirreza Gholami

Neuroscience Letters, Journal Year: 2023, Volume and Issue: 817, P. 137532 - 137532

Published: Oct. 20, 2023

Language: Английский

Citations

22
Nature's toolbox against tau aggregation: An updated review of current research DOI
Sumaiya Khan, Md. Imtaiyaz Hassan, Mohammad Shahid

et al.

Ageing Research Reviews, Journal Year: 2023, Volume and Issue: 87, P. 101924 - 101924

Published: March 31, 2023

Language: Английский

Citations

21
Protein diversification through post-translational modifications, alternative splicing, and gene duplication DOI Creative Commons
Yonathan Goldtzvik, Neeladri Sen, Su Datt Lam

et al.

Current Opinion in Structural Biology, Journal Year: 2023, Volume and Issue: 81, P. 102640 - 102640

Published: June 24, 2023

Proteins provide the basis for cellular function. Having multiple versions of same protein within a single organism provides way regulating its activity or developing novel functions. Post-translational modifications proteins, by means adding/removing chemical groups to amino acids, allow well-regulated and controlled generating functionally distinct species. Alternative splicing is another method with which organisms possibly generate new isoforms. Additionally, gene duplication events throughout evolution paralogs genes, resulting in an organism. In this review, we discuss recent advancements study these three methods diversification illustrative examples how they affect structure

Language: Английский

Citations

21
Impaired mitochondrial dynamics and removal of the damaged mitochondria in diabetic retinopathy DOI Creative Commons

Kumari Alka,

Jay Kumar, Renu A. Kowluru

et al.

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: June 21, 2023

Introduction Mitochondrial dynamic plays a major role in their quality control, and the damaged mitochondrial components are removed by autophagy. In diabetic retinopathy, fusion enzyme, mitofusin 2 (Mfn2), is downregulated disturbed resulting depolarized dysfunctional mitochondria. Our aim was to investigate mechanism of inhibition Mfn2, its removal mitochondria, retinopathy. Methods Using human retinal endothelial cells, effect high glucose (20mM) on GTPase activity Mfn2 acetylation were determined. Role mitochondria confirmed regulating acetylation, or overexpression, autophagosomes- autolysosomes formation mitophagy flux. Results High inhibited increased Mfn2. Inhibition attenuated decrease fragmentation, Similar phenomenon observed mice; overexpression sirtuin 1 (a deacetylase) ameliorated diabetes-induced facilitated Conclusions Acetylation has dual roles homeostasis it inhibits increases also impairs Thus, protecting should maintain inhibit development/progression

Language: Английский

Citations

17