PTEN Dual Lipid- and Protein-Phosphatase Function in Tumor Progression

Cancers, Journal Year: 2022, Volume and Issue: 14(15), P. 3666 - 3666

Published: July 28, 2022

PTEN is the second most highly mutated tumor suppressor in cancer, following only p53. The protein functions as a phosphatase with lipid- and protein-phosphatase activity. PTEN-lipid-phosphatase activity dephosphorylates PIP3 to form PIP2, it then antagonizes PI3K blocks activation of AKT, while its different substrates plays various roles tumorigenesis. Here, we review mutations tumorigenesis metastasis. Our purpose clarify how contributes tumor-suppressive through PI3K-independent activities.

Language: Английский

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Disturbing cytoskeleton by engineered nanomaterials for enhanced cancer therapeutics

Bioactive Materials, Journal Year: 2023, Volume and Issue: 29, P. 50 - 71

Published: June 29, 2023

Cytoskeleton plays a significant role in the shape change, migration, movement, adhesion, cytokinesis, and phagocytosis of tumor cells. In clinical practice, some anti-cancer drugs achieve cytoskeletal therapeutic effects by acting on different protein components. However, absence cell-specific targeting, unnecessary recombination organisms would be disastrous, which also bring about severe side during anticancer process. Nanomedicine have been proven to superior small molecule cancer treatment due better stability lower effects. Therefore, this review summarized recent developments various nanomaterials disturbing cytoskeleton for enhanced therapeutics, including carbon, noble metals, metal oxides, black phosphorus, calcium, silicon, polymers, peptides, metal-organic frameworks, etc. A comprehensive analysis characteristics therapy as well future prospects challenges towards application were discussed. We aim drive emerging topic through refreshing perspectives based our own work what we learnt from others. This will help researchers quickly understand relevant information further advance development nanomedicine.

Language: Английский

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14-3-3 proteins—a moonlight protein complex with therapeutic potential in neurological disorder: in-depth review with Alzheimer’s disease

Frontiers in Molecular Biosciences, Journal Year: 2024, Volume and Issue: 11

Published: Feb. 5, 2024

Alzheimer’s disease (AD) affects millions of people worldwide and is a gradually worsening neurodegenerative condition. The accumulation abnormal proteins, such as tau beta-amyloid, in the brain hallmark AD pathology. 14-3-3 proteins have been implicated pathology several ways. One proposed mechanism that interact with protein modulate its phosphorylation, aggregation, toxicity. Tau associated microtubules, playing role maintaining structural integrity neuronal cytoskeleton. However, context (AD), an increase phosphorylation occurs. This leads to aggregation into neurofibrillary tangles, which distinctive feature this Studies shown can bind phosphorylated regulate function stability. In addition, beta-amyloid (Aβ), primary component amyloid plaques AD. clearance Aβ through lysosomal degradation pathway by interacting membrane LAMP2A. Dysfunction thought contribute progression Furthermore, found be downregulated brains patients, suggesting their dysregulation may For example, decreased levels cerebrospinal fluid suggested biomarker for Overall, these findings suggest play important represent potential therapeutic target disease. further research needed fully understand mechanisms underlying involvement explore target.

Language: Английский

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Cytoskeletal dysregulation and neurodegenerative disease: Formation, monitoring, and inhibition of cofilin-actin rods

Frontiers in Cellular Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: Sept. 22, 2022

The presence of atypical cytoskeletal dynamics, structures, and associated morphologies is a common theme uniting numerous diseases developmental disorders. In particular, dysregulation cellular feature Alzheimer’s disease, Parkinson’s Huntington’s disease. While the activators inhibitors present complexities for characterizing these elements as byproducts or initiators disease state, it increasingly clear that better understanding anomalies critical advancing state knowledge plan therapeutic attack. this review, we focus on hallmarks are with cofilin-linked actin regulation, particular emphasis formation, monitoring, inhibition cofilin-actin rods. We also review actin-associated proteins other than cofilin links to cytoskeleton-associated neurodegenerative processes, recognizing rods comprise one strand vast web interactions occur result dysregulation. Our aim current perspective dysregulation, connecting recent developments in our emerging strategies biosensing biomimicry will help shape future directions field.

Language: Английский

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Biochemical Pathways of Cellular Mechanosensing/Mechanotransduction and Their Role in Neurodegenerative Diseases Pathogenesis

Cells, Journal Year: 2022, Volume and Issue: 11(19), P. 3093 - 3093

Published: Oct. 1, 2022

In this review, we shed light on recent advances regarding the characterization of biochemical pathways cellular mechanosensing and mechanotransduction with particular attention to their role in neurodegenerative disease pathogenesis. While mechanistic components these are mostly uncovered today, crosstalk between mechanical forces soluble intracellular signaling is still not fully elucidated. Here, recapitulate general concepts mechanobiology mechanisms that govern processes, examine stimuli response, highlighting effect organelles' homeostasis dysfunction. particular, discuss current knowledge about translation mechanosignaling into signaling, focusing those diseases encompass metabolic accumulation mutant proteins have as primary characteristics formation pathological aggregates, such Alzheimer's Disease, Huntington's Amyotrophic Lateral Sclerosis Parkinson's Disease. Overall, findings elucidate how may be crucial understand pathogenic underlying emphasize importance for identifying potential therapeutic targets.

Language: Английский

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The Multifaceted Role of Cofilin in Neurodegeneration and Stroke: Insights into Pathogenesis and Targeting as a Therapy

Cells, Journal Year: 2024, Volume and Issue: 13(2), P. 188 - 188

Published: Jan. 18, 2024

This comprehensive review explores the complex role of cofilin, an actin-binding protein, across various neurodegenerative diseases (Alzheimer’s, Parkinson’s, schizophrenia, amyotrophic lateral sclerosis (ALS), Huntington’s) and stroke. Cofilin is essential protein in cytoskeletal dynamics, any dysregulation could lead to potentially serious complications. Cofilin’s involvement underscored by its impact on pathological hallmarks like Aβ plaques α-synuclein aggregates, triggering synaptic dysfunction, dendritic spine loss, impaired neuronal plasticity, leading cognitive decline. In Parkinson’s disease, cofilin collaborates with α-synuclein, exacerbating neurotoxicity impairing mitochondrial axonal function. ALS frontotemporal dementia showcase cofilin’s association genetic factors C9ORF72, affecting actin dynamics contributing neurotoxicity. Huntington’s disease brings into focus microglial migration influencing plasticity through AMPA receptor regulation. Alzheimer’s, schizophrenia exhibit 14-3-3 proteins as a shared mechanism. case stroke, takes center stage, mediating cell death. Notably, there potential overlap pathologies diseases. this context, referencing dysfunction provide valuable insights common associated aforementioned conditions. Moreover, promising therapeutic interventions, including inhibitors gene therapy, demonstrating efficacy preclinical models. Challenges inhibitor development, brain delivery, tissue/cell specificity, long-term safety are acknowledged, emphasizing need for precision drug therapy. The call action involves collaborative research, biomarker identification, advancing translational efforts. emerges pivotal player, offering target. However, unraveling complexities requires concerted multidisciplinary efforts nuanced effective interventions intricate landscape presenting hopeful avenue improved patient care.

Language: Английский

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Role of Cyclins and Cytoskeletal Proteins in Endometriosis: Insights into Pathophysiology

Cancers, Journal Year: 2024, Volume and Issue: 16(4), P. 836 - 836

Published: Feb. 19, 2024

Endometriosis is a gynecological condition where endometrium-like tissue grows outside the uterus, posing challenges in understanding and treatment. This article delves into deep cellular molecular processes underlying endometriosis, with focus on crucial roles played by cyclins cytoskeletal proteins its pathogenesis, particularly context of Epithelial–Mesenchymal Transition (EMT). The investigation begins examining activities cyclins, elucidating their diverse biological such as cell cycle control, proliferation, evasion apoptosis, angiogenesis among ectopic endometrial cells. A comprehensive analysis follows, emphasizing fundamental specific significance to endometriotic features. review sheds light interconnected pathways through which converge, contributing genesis progression endometriosis. Understanding these complexities not only provides insight causes disease but also holds promise for development therapeutic approaches, ushering new era management this devastating disorder.

Language: Английский

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A glimpse into cofilin-1 role in cancer therapy: A potential target to improve clinical outcomes?

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(2), P. 189087 - 189087

Published: Feb. 22, 2024

Language: Английский

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α-Synuclein triggers cofilin pathology and dendritic spine impairment via a PrPC-CCR5 dependent pathway

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(4)

Published: April 13, 2024

Abstract Cognitive dysfunction and dementia are critical symptoms of Lewy Body dementias (LBD). Specifically, alpha-synuclein (αSyn) accumulation in the hippocampus leading to synaptic is linked cognitive deficits LBD. Here, we investigated pathological impact αSyn on hippocampal neurons. We report that either overexpression or pre-formed fibrils (PFFs) treatment triggers formation cofilin-actin rods, synapse disruptors, cultured neurons synucleinopathy mouse models LBD patients. In vivo, cofilin pathology present concomitantly with impairment dysfunction. Rods generation prompted by involves co-action cellular prion protein (PrP C ) chemokine receptor 5 (CCR5). Importantly, show CCR5 inhibition, a clinically relevant peptide antagonist, reverts dendritic spine promoted αSyn. Collectively, detail molecular mechanism through which disrupts structure identify as novel therapeutic target prevent

Language: Английский

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Chromatin meets the cytoskeleton: the importance of nuclear actin dynamics and associated motors for genome stability

DNA repair, Journal Year: 2023, Volume and Issue: 131, P. 103571 - 103571

Published: Sept. 16, 2023

The actin cytoskeleton is of fundamental importance for numerous cellular processes, including intracellular transport, cell plasticity, and migration. However, functions filamentous (F-actin) in the nucleus remain understudied due to comparatively low abundance nuclear resulting experimental limitations its visualization. Owing recent technological advances such as super-resolution microscopy development nuclear-specific probes, essential roles context genome maintenance are now emerging. In addition contributions monomeric a component multiple important protein complexes, has been found undergo polymerization response DNA damage replication stress. Consequently, F-actin plays regulation intra-nuclear mobility repair foci well shape, two aspects efficient stress tolerance. Beyond itself, there accumulating evidence participation actin-binding proteins (ABPs) surveillance integrity, nucleation factors motor myosin family. Here we summarize findings highlighting cytoskeletal within key pathways.

Language: Английский

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