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Past, present, and future of serotonin-targeting therapeutics for Alzheimer's disease: Perspectives from DNA methylation

8 months 1 week ago
With population aging, Alzheimer's disease (AD) is becoming increasingly prevalent, causing great health and economic burdens worldwide. Despite decades of research, there are still no effective disease-modifying treatments for AD, highlighting the urgent need for more in-depth understanding of the disease-causing mechanisms. The brain serotonin (5-HT) neurotransmission system undergoes structural and functional changes in aging and AD, which contributes to cognitive decline and comorbid mood...
Yanzhi Liu

Phase I/II trial of iPS-cell-derived dopaminergic cells for Parkinson's disease

8 months 1 week ago
Parkinson's disease is caused by the loss of dopamine neurons, causing motor symptoms. Initial cell therapies using fetal tissues showed promise but had complications and ethical concerns^(1-5). Pluripotent stem (PS) cells emerged as a promising alternative for developing safe and effective treatments⁶. In this phase I/II trial at Kyoto University Hospital, seven patients (ages 50-69) received bilateral transplantation of dopaminergic progenitors derived from induced PS (iPS) cells. Primary...
Nobukatsu Sawamoto

Phase I trial of hES cell-derived dopaminergic neurons for Parkinson's disease

8 months 1 week ago
Parkinson's disease is a progressive neurodegenerative condition with a considerable health and economic burden¹. It is characterized by the loss of midbrain dopaminergic neurons and a diminished response to symptomatic medical or surgical therapy as the disease progresses². Cell therapy aims to replenish lost dopaminergic neurons and their striatal projections by intrastriatal grafting. Here, we report the results of an open-label phase I clinical trial (NCT04802733) of an investigational...
V Tabar

Dynamics and role of covalently-closed circular RNAs in Alzheimer's disease: A review of experimental and bioinformatics studies

8 months 1 week ago
Alzheimer's disease (AD) is an age-associated disorder characterized by cognitive decline, with dementia representing the final stage of a complex clinical-biological process rather than simply a more severe form of cognitive decline. Circular RNAs (circRNAs), novel non-coding RNAs, have emerged as key regulators of brain function and associated disorders. This study explores the role of circRNAs in AD by reviewing experimentally validated circRNAs in human and animal models. We identified 10...
Nikta Zafarjafarzadeh

Past, present, and future of serotonin-targeting therapeutics for Alzheimer's disease: Perspectives from DNA methylation

8 months 1 week ago
With population aging, Alzheimer's disease (AD) is becoming increasingly prevalent, causing great health and economic burdens worldwide. Despite decades of research, there are still no effective disease-modifying treatments for AD, highlighting the urgent need for more in-depth understanding of the disease-causing mechanisms. The brain serotonin (5-HT) neurotransmission system undergoes structural and functional changes in aging and AD, which contributes to cognitive decline and comorbid mood...
Yanzhi Liu

scPRINT: pre-training on 50 million cells allows robust gene network predictions

8 months 1 week ago
A cell is governed by the interaction of myriads of macromolecules. Inferring such a network of interactions has remained an elusive milestone in cellular biology. Building on recent advances in large foundation models and their ability to learn without supervision, we present scPRINT, a large cell model for the inference of gene networks pre-trained on more than 50 million cells from the cellxgene database. Using innovative pretraining tasks and model architecture, scPRINT pushes large...
Jérémie Kalfon

Effects of life-long hyperlipidaemia on age-dependent development of endothelial dysfunction in humanised dyslipidaemic mice

8 months 1 week ago
Little is known, how life-long hyperlipidaemia affects vascular ageing, before atherosclerosis. Here, we characterise effects of mild, life-long hyperlipidaemia on age-dependent endothelial dysfunction (ED) in humanised dyslipidaemia model of E3L.CETP mice. Vascular function was characterised using magnetic resonance imaging in vivo and wire myograph ex vivo. Plasma endothelial biomarkers and non-targeted proteomics in plasma and aorta were analysed. Early atherosclerosis lesions were...
Anna Bar

Elevated mitochondrial membrane potential is a therapeutic vulnerability in Dnmt3a-mutant clonal hematopoiesis

8 months 1 week ago
The competitive advantage of mutant hematopoietic stem and progenitor cells (HSPCs) underlies clonal hematopoiesis (CH). Drivers of CH include aging and inflammation; however, how CH-mutant cells gain a selective advantage in these contexts is an unresolved question. Using a murine model of CH (Dnmt3a^(R878H/+)), we discover that mutant HSPCs sustain elevated mitochondrial respiration which is associated with their resistance to aging-related changes in the bone marrow microenvironment. Mutant...
Kira A Young