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The mechanism of cuproptosis in Parkinson's disease

3 months 1 week ago
Parkinson's disease (PD) is a neurodegenerative disease with an increased morbidity. The pathogenesis PD has not been fully elucidated, and whatever mechanism is involved, it ultimately leads to dopamine (DA) neuronal apoptosis. Cuproptosis is a novel form of cell death. Its morphology, biochemical properties, and mechanism of action differ from known forms of cell death, such as apoptosis, autophagy, necrosis and pyroptosis. Copper binds to the lipoylated components of the tricarboxylic acid...
Min Huang

Local structural preferences in shaping tau amyloid polymorphism

3 months 1 week ago
Tauopathies encompass a group of neurodegenerative disorders characterised by diverse tau amyloid fibril structures. The persistence of polymorphism across tauopathies suggests that distinct pathological conditions dictate the adopted polymorph for each disease. However, the extent to which intrinsic structural tendencies of tau amyloid cores contribute to fibril polymorphism remains uncertain. Using a combination of experimental approaches, we here identify a new amyloidogenic motif, PAM4...
Nikolaos Louros

Senescent cells and macrophages cooperate through a multi-kinase signaling network to promote intestinal transformation in Drosophila

3 months 1 week ago
Cellular senescence is a conserved biological process that plays a crucial and context-dependent role in cancer. The highly heterogeneous and dynamic nature of senescent cells and their small numbers in tissues make in vivo mechanistic studies of senescence challenging. As a result, how multiple senescence-inducing signals are integrated in vivo to drive senescence in only a small number of cells is unclear. Here, we identify cells that exhibit multiple features of senescence in a Drosophila...
Ishwaree Datta

Pharmacological interventions in human aging

3 months 1 week ago
Pharmacological interventions are emerging as potential avenues of alleviating age-related disease. However, the knowledge of ongoing clinical trials as they relate to aging and pharmacological interventions is dispersed across a variety of mediums. In this review we summarize 136 age-related clinical trials that have been completed or are ongoing. Furthermore, we establish a database that describe the trials (AgingDB, www.agingdb.com) keeping track of the previous and ongoing clinical trials,...
Michael Angelo Petr

ANKRD1 is a mesenchymal-specific driver of cancer-associated fibroblast activation bridging androgen receptor loss to AP-1 activation

3 months 1 week ago
There are significant commonalities among several pathologies involving fibroblasts, ranging from auto-immune diseases to fibrosis and cancer. Early steps in cancer development and progression are closely linked to fibroblast senescence and transformation into tumor-promoting cancer-associated fibroblasts (CAFs), suppressed by the androgen receptor (AR). Here, we identify ANKRD1 as a mesenchymal-specific transcriptional coregulator under direct AR negative control in human dermal fibroblasts...
Luigi Mazzeo

Detection of senescence using machine learning algorithms based on nuclear features

3 months 1 week ago
Cellular senescence is a stress response with broad pathophysiological implications. Senotherapies can induce senescence to treat cancer or eliminate senescent cells to ameliorate ageing and age-related pathologies. However, the success of senotherapies is limited by the lack of reliable ways to identify senescence. Here, we use nuclear morphology features of senescent cells to devise machine-learning classifiers that accurately predict senescence induced by diverse stressors in different cell...
Imanol Duran

Psychedelics for Alzheimer's Disease-Related Dementia: Unveiling Therapeutic Possibilities and Pathways

3 months 2 weeks ago
Psychedelics have traditionally been used for spiritual and recreational purposes, but recent developments in psychotherapy have highlighted their potential as therapeutic agents. These compounds, which act as potent 5-hydroxytryptamine (5HT) agonists, have been recognized for their ability to enhance neural plasticity through the activation of the serotoninergic and glutamatergic systems. However, the implications of these findings for the treatment of neurodegenerative disorders, particularly...
Jitendra Kumar Sinha

Early onset diagnosis in Alzheimer's disease patients via amyloid-beta oligomers-sensing probe in cerebrospinal fluid

3 months 2 weeks ago
Amyloid-β (Aβ) oligomers are implicated in the onset of Alzheimer's disease (AD). Herein, quinoline-derived half-curcumin-dioxaborine (Q-OB) fluorescent probe was designed for detecting Aβ oligomers by finely tailoring the hydrophobicity of the biannulate donor motifs in donor-π-acceptor structure. Q-OB shows a great sensing potency in dynamically monitoring oligomerization of Aβ during amyloid fibrillogenesis in vitro. In addition, we applied this strategy to fluorometrically analyze Aβ...
Jusung An

Unraveling the brain's response to COVID-19: How SARS-CoV-2 afflicts dopaminergic neurons

3 months 2 weeks ago
COVID-19 patients often display dysfunctions of the nervous system, indicating an effect of SARS-CoV-2 on neural cells. Yang et al. now show that human stem-cell-derived dopaminergic neurons are susceptible to SARS-CoV-2, triggering inflammation and senescence. The study further identifies three FDA-approved drugs capable of reversing these cellular phenotypes.
Ilse Eidhof

Breaking the links between ageism and health: An integrated perspective

3 months 2 weeks ago
Ageism refers to prejudice, stereotypes or discrimination based on a person's actual or perceived chronological age. While ageism can affect people at all stages of the human lifespan, ageism against older adults has emerged as the most pervasive and potentially harmful. Much is now understood about how ageism can impact older people's health and wellbeing via structural, organisational, and provider level biases that threaten the provision of equitable and ethical healthcare. Negative attitudes...
Julie D Henry

Optimizing potassium polysulfides for high performance potassium-sulfur batteries

3 months 2 weeks ago
Potassium-sulfur batteries attract tremendous attention as high-energy and low-cost energy storage system, but achieving high utilization and long-term cycling of sulfur remains challenging. Here we show a strategy of optimizing potassium polysulfides for building high-performance potassium-sulfur batteries. We design the composite of tungsten single atom and tungsten carbide possessing potassium polysulfide migration/conversion bi-functionality by theoretical screening. We create two ligand...
Wanqing Song

The SATB1-MIR22-GBA axis mediates glucocerebroside accumulation inducing a cellular senescence-like phenotype in dopaminergic neurons

3 months 2 weeks ago
Idiopathic Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, which is associated with neuroinflammation and reactive gliosis. The underlying cause of PD and the concurrent neuroinflammation are not well understood. In this study, we utilize human and murine neuronal lines, stem cell-derived dopaminergic neurons, and mice to demonstrate that three previously identified genetic risk factors for PD, namely SATB1, MIR22HG, and GBA,...
Taylor Russo

The SATB1-MIR22-GBA axis mediates glucocerebroside accumulation inducing a cellular senescence-like phenotype in dopaminergic neurons

3 months 2 weeks ago
Idiopathic Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, which is associated with neuroinflammation and reactive gliosis. The underlying cause of PD and the concurrent neuroinflammation are not well understood. In this study, we utilize human and murine neuronal lines, stem cell-derived dopaminergic neurons, and mice to demonstrate that three previously identified genetic risk factors for PD, namely SATB1, MIR22HG, and GBA,...
Taylor Russo

Xrp1 governs the stress response program to spliceosome dysfunction

3 months 2 weeks ago
Co-transcriptional processing of nascent pre-mRNAs by the spliceosome is vital to regulating gene expression and maintaining genome integrity. Here, we show that the deficiency of functional U5 small nuclear ribonucleoprotein particles (snRNPs) in Drosophila imaginal cells causes extensive transcriptome remodeling and accumulation of highly mutagenic R-loops, triggering a robust stress response and cell cycle arrest. Despite compromised proliferative capacity, the U5 snRNP-deficient cells...
Dimitrije Stanković