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Heat-shock chaperone HSPB1 mitigates poly-glycine-induced neurodegeneration via restoration of autophagic flux

1 month 2 weeks ago
The CGG repeat expansions in the 5'-UTR regions of certain genes have been implicated in various neurodegenerative and muscular disorders. However, the underlying pathogenic mechanisms are not well understood. In this study, we explore the role of the small molecular chaperone HSPB1 in counteracting neurodegeneration induced by poly-glycine (poly-G) aggregates. Employing a reporter system, we demonstrate that CGG repeat expansions within the 5'-UTR of the GIPC1 gene produce poly-G proteins, by...
Ning Ding

Soluble cerebral Abeta protofibrils link Abeta plaque pathology to changes in CSF Abeta(42)/Abeta(40) ratios, neurofilament light and tau in Alzheimer's disease model mice

1 month 2 weeks ago
The Aβ(42)/Aβ(40) ratio in the cerebrospinal fluid (CSF) and the concentrations of neurofilament light (NfL) and total tau (t-tau) are changed in the early stages of Alzheimer's disease (AD)¹, but their neurobiological correlates are not entirely understood. Here, we used 5xFAD transgenic mice to investigate the associations between these CSF biomarkers and measures of cerebral Aβ, including Aβ(42)/Aβ(40) ratios in plaques, insoluble fibrillar deposits and soluble protofibrils. A high...
Emelie Andersson

Neurobiological role and therapeutic potential of exercise-induced irisin in Alzheimer's disease management

1 month 2 weeks ago
Alzheimer's disease (AD) poses a significant obstacle in today's healthcare landscape, with limited effective treatments. Recent studies have revealed encouraging findings about how exercise-triggered irisin might help slow down the advancement of AD. Irisin, a myokine, released during physical activity, has garnered significant attention for its pleiotropic effects, extending beyond its traditional role in metabolic regulation. This review explores irisin's multifaceted potential in combating...
Nandini Ratne

Everything everywhere all at once: Unraveling the waves of aging

1 month 2 weeks ago
In a recent work reported in Science, Zhang et al. untangle dynamic changes arising across aging in multiple cell populations within thirteen organs using single-cell transcriptomics and identify four distinct dynamic waves in which immune cells are the most affected populations.
Jose Ignacio Escrig-Larena

Isoform usage as a distinct regulatory layer driving nutrient-responsive metabolic adaptation

1 month 2 weeks ago
Transcriptome modulation is essential for metabolic adaptation to nutrient environments. However, the role of isoform usage, a crucial transcriptome component, is not yet fully understood. This study outlines the landscape of isoform-usage modulations across major metabolic organs in both mice and monkeys, spanning diverse metabolic states. Our in-depth analysis identifies numerous isoform-usage events, intricately influenced by nutrient challenges and largely independent of gene expression...
Jia Li

Adipose chemokine ligand CX3CL1 contributes to maintaining the hippocampal BDNF level, and the effect is attenuated in advanced age

1 month 2 weeks ago
Aging alters signaling that involves brain-derived neurotrophic factor (BDNF) in the hippocampus. An adequate level of BDNF is essential for maintaining cognitive function in older adults. Previously, we showed that repeated intraperitoneal administration of the chemokine ligand CX3CL1 modulates peritoneal immune cells and the vagal nerve to increase hippocampal BDNF, consequently improving cognitive decline in aged mice. Here, we examined the contribution of endogenous CX3CL1 in the peritoneal...
Yoshinori Takei

Balanced plant helper NLR activation by a modified host protein complex

1 month 2 weeks ago
Nucleotide-binding leucine-rich repeat (NLR) receptors play crucial roles in plant immunity by sensing pathogen effectors¹. In Arabidopsis, certain sensor NLRs function as NADases to catalyse the production of second messengers^(2,3), which can be recognized by enhanced disease susceptibility 1 (EDS1) with its partner senescence-associated gene 101 (SAG101), to activate helper NLR N requirement gene 1 (NRG1)⁴. A cryoelectron microscopy structure shows that second-messenger-activated EDS1-SAG101...
Shijia Huang

Shielding Pt/γ-Mo<sub>2</sub>N by inert nano-overlays enables stable H<sub>2</sub> production

1 month 2 weeks ago
The use of reactive supports to disperse metal species is crucial for constructing highly efficient interfacial catalysts, by tuning the competitive reactant adsorption-activation pattern in supported metal catalysts into a non-competitive mechanism^(1-3). However, these reactive supports are prone to deterioration during catalysis, limiting the lifespan of the catalyst and their potential practical applications⁴. New strategies are needed to simultaneously protect reactive supports and surface...
Zirui Gao

Early-age efferocytosis directs macrophage arachidonic acid metabolism for tissue regeneration

1 month 2 weeks ago
In response to organ injury in adults, macrophages often promote scarring, yet during early life, they are required for tissue regeneration. To elucidate the mechanisms underlying age-associated regeneration, we compared the macrophage injury response in newborn versus adult hearts. Single-cell analysis revealed an accumulation of tissue-resident macrophages in neonates that were selectively polarized for apoptotic cell recognition and uptake (efferocytosis). Ablation of the apoptotic cell...
Connor Lantz

Neutrophil-derived vesicles control complement activation to facilitate inflammation resolution

1 month 2 weeks ago
Although subsets with immunosuppressive properties exist, neutrophils are typically known for their pro-inflammatory role and pathogen clearance capabilities. Here, we reveal that neutrophils can paradoxically aid in resolving inflammation by actively producing anti-inflammatory extracellular vesicles. These large aging-neutrophil-derived vesicles (LAND-Vs) do not fit into classical vesicle categorizations due to their specific size, structure, or biogenesis pathway. They are protected from...
Alan Y Hsu