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Dual-Lineage Chondrocyte-Like Cells in the Nucleus Pulposus of Aging Intervertebral Discs Are Accelerated by Hedgehog Signaling Inactivation

9 months ago
Intervertebral disc (IVD) degeneration, a major contributor to chronic low back pain, is characterized by the age-related replacement of notochord-derived nucleus pulposus cells (NPCs) with chondrocyte-like or fibrotic cells (CLCs). However, the cellular origins of CLCs and mechanisms driving their emergence remain contentious. Using genetic lineage tracing with Shh-Cre and Gli1-CreER^(T2) to track notochordal and non-notochordal cells, respectively, we demonstrate that CLCs arise from dual...
Lei Zhang

DJ-1/PARK7 in Parkinson's disease: mechanisms of pathogenesis and therapeutic potential

9 months ago
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, characterized by the substantial degeneration of nigral dopaminergic neurons, the accumulation of alpha-synuclein, and the intraneuronal formation of Lewy bodies. DJ-1 is a multifaceted protein that has been linked to the pathogenesis of neurodegenerative diseases. Recent research has highlighted a potential role for DJ-1 in PD. This protein plays a critical role in maintaining mitochondrial homeostasis, modulating...
Weicong Bao

Correlation of adult neurogenesis and cognitive performance in touchscreen tasks - assessing the novel small molecule OXS-N1 in mice

9 months ago
Adult hippocampal neurogenesis in the dentate gyrus is well-defined in rodents, and its role in cognitive functions as well as its potential as a therapeutic target for neurodegenerative diseases such as Alzheimer's disease remain a topic of great scientific interest. In this study, we evaluated the effects of a novel small molecule, OXS-N1, on neurogenesis and behavior in C57Bl/6 wild-type and 5xFAD Alzheimer's disease model mice, which were tested independently at different ages. Modern,...
Joel Melcop

Telomeric DNA damage response mediates neurotoxicity of Abeta42 oligomers in Alzheimer's disease

9 months ago
Ageing is the major risk factor for Alzheimer's disease (AD), the most common neurodegenerative disorder. DNA damage is a hallmark of ageing, particularly when occurring at telomeres, genomic regions vulnerable to oxidative damage and often challenging for the cell to repair. Here, we show that brains of 3xTg-AD mice, an established AD model characterized by amyloid-β (Aβ)-induced pathology, exhibit increased activation of DNA damage response (DDR) pathways at telomeres. Exposure of mouse...
Sara Sepe

Telomeric DNA damage response mediates neurotoxicity of Aβ42 oligomers in Alzheimer's disease

9 months ago
Ageing is the major risk factor for Alzheimer's disease (AD), the most common neurodegenerative disorder. DNA damage is a hallmark of ageing, particularly when occurring at telomeres, genomic regions vulnerable to oxidative damage and often challenging for the cell to repair. Here, we show that brains of 3xTg-AD mice, an established AD model characterized by amyloid-β (Aβ)-induced pathology, exhibit increased activation of DNA damage response (DDR) pathways at telomeres. Exposure of mouse...
Sara Sepe

Integrating artificial intelligence with small molecule therapeutics and precision medicine for neurochemical understanding of Alzheimer's diseases

9 months ago
Alzheimer's disease (AD) is the most common neurodegenerative condition and continues to pose significant clinical and research challenges due to its complex causes and limited treatment success. Conventional therapies have primarily focused on amyloid-beta (Aβ) and tau proteins, but these efforts have yet to produce optimal results. This review explores emerging interdisciplinary strategies that integrate artificial intelligence (AI), small molecule drugs, and precision treatments to tackle...
Zafer Saad Alshehri