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Does drug repurposing bridge the gaps in management of Parkinson's disease? Unravelling the facts and fallacies

7 months ago
Repurposing the existing drugs for the management of both common and rare diseases is increasingly appealing due to challenges such as high attrition rates, the economy, and the slow pace of discovering new drugs. Drug repurposing involves the utilization of existing medications to treat diseases for which they were not originally intended. Despite encountering scientific and economic challenges, the pharmaceutical industry is intrigued by the potential to uncover new indications for...
Bushra Bashir

Exploring morphological and microstructural signatures across the Alzheimer's spectrum and risk factors

7 months ago
Neural alterations, including myelin degeneration and inflammation-related iron burden, may accompany early Alzheimer's disease (AD) pathophysiology. This study aims to identify multi-modal signatures associated with MRI-derived atrophy and quantitative MRI (qMRI) measures of myelin and iron in a unique dataset of 158 participants across the AD spectrum, including those without cognitive impairment, at familial risk for AD, with mild cognitive impairment, and with AD dementia. Our results...
Aurélie Bussy

Cell enlargement modulated by GATA4 and YAP instructs the senescence-associated secretory phenotype

7 months ago
Dynamic changes in cell size are associated with development and pathological conditions, including aging. Although cell enlargement is a prominent morphological feature of cellular senescence, its functional implications are unknown; moreover, how senescent cells maintain their enlargement state is less understood. Here we show that an extensive remodeling of actin cytoskeleton is necessary for establishing senescence-associated cell enlargement and pro-inflammatory senescence-associated...
Joae Joung

BMP signaling promotes zebrafish heart regeneration via alleviation of replication stress

7 months ago
In contrast to mammals, adult zebrafish achieve complete heart regeneration via proliferation of cardiomyocytes. Surprisingly, we found that regenerating cardiomyocytes experience DNA replication stress, which represents one reason for declining tissue regeneration during aging in mammals. Pharmacological inhibition of ATM and ATR kinases revealed that DNA damage response signaling is essential for zebrafish heart regeneration. Manipulation of Bone Morphogenetic Protein (BMP)-Smad signaling...
Mohankrishna Dalvoy Vasudevarao

Behavioural pharmacology predicts disrupted signalling pathways and candidate therapeutics from zebrafish mutants of Alzheimer's disease risk genes

7 months ago
By exposing genes associated with disease, genomic studies provide hundreds of starting points that should lead to druggable processes. However, our ability to systematically translate these genomic findings into biological pathways remains limited. Here, we combine rapid loss-of-function mutagenesis of Alzheimer's risk genes and behavioural pharmacology in zebrafish to predict disrupted processes and candidate therapeutics. FramebyFrame, our expanded package for the analysis of larval...
François Kroll

Hybrid immunity-based induction of durable pan-endemic-coronavirus immunity in the elderly

7 months ago
Repeated vaccinations and infections have led to diverse states of hybrid immunity against SARS-CoV-2 in the global population. However, age and comorbidities can compromise protection against severe disease, and antibody-mediated immunity is undercut by viral immune escape mutations. Whether and to what extent durable T cell responses compensate for reduced humoral immunity, particularly in the elderly, have not been investigated. Here, we utilize SARS-CoV-2-specific and pan-coronavirus-derived...
Lucie Loyal

Activated mTOR Signaling in the RPE Drives EMT, Autophagy, and Metabolic Disruption, Resulting in AMD-Like Pathology in Mice

7 months ago
The mechanistic target of rapamycin (mTOR) complexes 1 and 2 (mTORC1/2) are crucial for various physiological functions. Although the role of mTORC1 in retinal pigmented epithelium (RPE) homeostasis and age-related macular degeneration (AMD) pathogenesis is established, the function of mTORC2 remains unclear. We investigated both complexes in RPE health and disease. Therefore, in this study, we have attempted to demonstrate that the specific overexpression of mammalian lethal with Sec13 protein...
Olivia Chowdhury

The Impact of Toll-Like Receptor 5 on Liver Function in Age-Related Metabolic Disorders

7 months ago
Toll-like receptor 5 (TLR5) plays a critical role beyond its traditional function in innate immunity, significantly impacting metabolic regulation and liver health. Previously, we reported that TLR5 activation extends the healthspan and lifespan of aging mice. This study demonstrates that TLR5 deficiency leads to pronounced metabolic abnormalities with age, primarily affecting liver metabolic functions rather than intestinal inflammation. Comprehensive RNA sequencing analysis revealed that TLR5...
Dong-Hyun Kim

The Antiaging and Antioxidative Effects of a Combination of Resveratrol and High-Intensity Interval Training on the Frontal Lobe in Aged Rats: The Role of SIRTS 4, SIRTS 5, SOD1, and SOD2

7 months ago
Introduction: High-intensity interval training (HIIT) is a form of interval exercise that enhances capacity and benefits well-being. Resveratrol is a naturally occurring polyphenol prevalent in grapes and red wine, demonstrating significant health effects on the body. This study sought to evaluate the synergistic effects of swimming HIIT and resveratrol intake on the expression of SIRTs 4, SIRTs 5, and superoxide dismutases (SOD1 and SOD2) in the frontal lobe of elderly rats. Materials and...
Amin Mehrabi