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Genentech, Sangamo ink Alzheimer's deal
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RTP801 interacts with the tRNA ligase complex and dysregulates its RNA ligase activity in Alzheimer's disease
RTP801/REDD1 is a stress-responsive protein overexpressed in neurodegenerative diseases such as Alzheimer's disease (AD) that contributes to cognitive deficits and neuroinflammation. Here, we found that RTP801 interacts with HSPC117, DDX1 and CGI-99, three members of the tRNA ligase complex (tRNA-LC), which ligates the excised exons of intron-containing tRNAs and the mRNA exons of the transcription factor XBP1 during the unfolded protein response (UPR). We also found that RTP801 modulates the...
Extracellular vesicle-encapsulated miR-30c-5p reduces aging-related liver fibrosis
Aging is associated with decreased health span, and despite the recent advances made in understanding the mechanisms of aging, no antiaging drug has been approved for therapy. Therefore, strategies to promote a healthy life in aging are desirable. Previous work has shown that chronic treatment with extracellular vesicles (EVs) from young mice prolongs lifespan in old mice, but the mechanism of action of this effect on liver metabolism is not known. Here we investigated the role of treatment with...
Metformin decelerates aging clock in male monkeys
In a rigorous 40-month study, we evaluated the geroprotective effects of metformin on adult male cynomolgus monkeys, addressing a gap in primate aging research. The study encompassed a comprehensive suite of physiological, imaging, histological, and molecular evaluations, substantiating metformin's influence on delaying age-related phenotypes at the organismal level. Specifically, we leveraged pan-tissue transcriptomics, DNA methylomics, plasma proteomics, and metabolomics to develop innovative...
IRescue: uncertainty-aware quantification of transposable elements expression at single cell level
Transposable elements (TEs) are mobile DNA repeats known to shape the evolution of eukaryotic genomes. In complex organisms, they exhibit tissue-specific transcription. However, understanding their role in cellular diversity across most tissues remains a challenge, when employing single-cell RNA sequencing (scRNA-seq), due to their widespread presence and genetic similarity. To address this, we present IRescue (Interspersed Repeats single-cell quantifier), a software capable of estimating the...
Catchers of folding gone awry: a tale of small heat shock proteins
Small heat shock proteins (sHsps) are an important part of the cellular system maintaining protein homeostasis under physiological and stress conditions. As molecular chaperones, they form complexes with different non-native proteins in an ATP-independent manner. Many sHsps populate ensembles of energetically similar but different-sized oligomers. Regulation of chaperone activity occurs by changing the equilibrium of these ensembles. This makes sHsps a versatile and adaptive system for trapping...
Exploiting the mechanical effects of ultrasound for noninvasive therapy
Science, Volume 385, Issue 6714, September 2024.
Durably reducing conspiracy beliefs through dialogues with AI
Science, Volume 385, Issue 6714, September 2024.
Autoregulated splicing of TRA2β programs T cell fate in response to antigen-receptor stimulation
Science, Volume 385, Issue 6714, September 2024.
Microbial dietary preference and interactions affect the export of lipids to the deep ocean
Science, Volume 385, Issue 6714, September 2024.
Transcripts of repetitive DNA elements signal to block phagocytosis of hematopoietic stem cells
Science, Volume 385, Issue 6714, September 2024.
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Midnolin, a Genetic Risk Factor for Parkinson's Disease, Promotes Neurite Outgrowth Accompanied by Early Growth Response 1 Activation in PC12 Cells
Parkinson's disease (PD) is an age-related progressive neurodegenerative disease. Previously, we identified midnolin (MIDN) as a genetic risk factor for PD. Although MIDN copy number loss increases the risk of PD, the molecular function of MIDN remains unclear. To investigate the role of MIDN in PD, we established monoclonal Midn knockout (KO) PC12 cell models. Midn KO inhibited neurite outgrowth and neurofilament light chain (Nefl) gene expression. Although MIDN is mainly localized in the...
Altered firing output of VIP interneurons and early dysfunctions in CA1 hippocampal circuits in the 3xTg mouse model of Alzheimer's disease
Alzheimer's disease (AD) leads to progressive memory decline, and alterations in hippocampal function are among the earliest pathological features observed in human and animal studies. GABAergic interneurons (INs) within the hippocampus coordinate network activity, among which type 3 interneuron-specific (I-S3) cells expressing vasoactive intestinal polypeptide and calretinin play a crucial role. These cells provide primarily disinhibition to principal excitatory cells (PCs) in the hippocampal...
Remember oligodendrocytes: Uncovering their overlooked role in Alzheimer's disease
Our understanding of Alzheimer's disease (AD) has evolved from focusing solely on neurons to recognizing the role of glia. A recent study in PLOS Biology revealed that oligodendrocytes are an important source of Aβ that impairs neuronal function.