Evidence for a role of human blood-borne factors in mediating age-associated changes in molecular circadian rhythms DOI Creative Commons
Jessica E. Schwarz,

Antonijo Mrčela,

Nicholas F. Lahens

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: July 18, 2023

Aging is associated with a number of physiologic changes including perturbed circadian rhythms; however, mechanisms by which rhythms are altered remain unknown. To test the idea that circulating factors mediate age-dependent in peripheral rhythms, we compared ability human serum from young and old individuals to synchronize culture. We collected blood apparently healthy (age 25–30) 70–76) at 14:00 used cultured fibroblasts. found sera equally competent initiating robust ~24 hr oscillations luciferase reporter driven clock gene promoter. However, cyclic expression affected, such promote cycling different sets genes. Genes lose rhythmicity entrainment oxidative phosphorylation Alzheimer’s Disease as identified STRING IPA analyses. Conversely, genes cholesterol biosynthesis increased cells entrained serum. involved cell cycle transcription/translation rhythmic both conditions. did not observe global difference distribution phase between groups, but peak several clock-controlled ( PER3, NR1D1, NR1D2, CRY1, CRY2, TEF ) lagged synchronized ex vivo Taken together, these findings demonstrate blood-borne affect have potential impact health disease via maintaining or disrupting respectively.

Language: Английский

Advancing Alzheimer’s Research With Zebrafish Models: Current Insights, Addressing Challenges, and Charting Future Courses DOI Open Access

Shreya Dey,

Tamilanban Thamaraikani,

Chitra Vellapandian

et al.

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 15, 2024

Alzheimer's disease (AD) is a neurological condition that progressively impairs cognitive function and results in memory loss. Despite substantial research efforts, little known about the specific processes driving AD, there are few proven therapies. Because of their physiological genetic resemblance to humans, zebrafish (Danio rerio) have become an important model organism for furthering on AD. This abstract discusses difficulties faced, looks at insights currently garnered from models, suggests future options. AD knowledge has greatly benefited use models. Transgenic express human AD-associated genes, such as tau amyloid precursor protein (APP), display neurofibrillary tangles (NFTs) amyloid-beta (Aβ) plaques, two disease's main clinical characteristics. These models clarified roles oxidative stress, inflammation, calcium homeostasis course allowed purpose high-throughput screening potential therapeutic agents. Understanding growth deterioration neurons been aided by real-time imaging. Fully using requires addressing number issues. The dissimilarities anatomy physiology difficulty developing replicate progressive late-onset (LOAD), requirement standardized procedures evaluate alterations cognition behavior Furthermore, variations makeup strains might affect experiments. Future directions include behavioral assays tests, working together create extensive databases phenotypic data, engineering techniques like CRISPR/Cas9 more complex Combining with other species helps expedite conversion into applications offers thorough To sum up, made contribution offering insightful information causes illness possible By tackling present issues formulating planned path, we can improve decipher mysteries help successful treatments.

Language: Английский

Citations

1
Pathophysiology of Alzheimer’s disease: an insight into the genetic factors, hypotheses, redox imbalance, and antioxidant intervention DOI
Teslim Simisola Abdulkadir, Joseph Olusegun Ayo

Comparative Clinical Pathology, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 13, 2024

Language: Английский

Citations

1
Identification of nitric oxide-mediated necroptosis as the predominant death route in Parkinson’s disease DOI Creative Commons
Ting Zhang,

Wenjing Rui,

Yue Sun

et al.

Molecular Biomedicine, Journal Year: 2024, Volume and Issue: 5(1)

Published: Oct. 24, 2024

Parkinson's disease (PD) involves multiple forms of neuronal cell death, but the dominant pathway involved in progression remains unclear. This study employed RNA sequencing (RNA-seq) brain tissue to explore gene expression patterns across different stages PD. Using Scaden deep learning algorithm, we predicted neurocyte subtypes and modelled dynamic interactions for five classic death pathways identify predominant routes during PD progression. Our type-specific analysis revealed an increasing shift towards necroptosis, which was strongly correlated with nitric oxide synthase (NOS) most subtypes. In vitro experiments confirmed that (NO) is a key mediator leading nuclear shrinkage decreased mitochondrial membrane potential via phosphorylation PIP1/PIP3/MLKL signalling cascade. Importantly, specific necroptosis inhibitors significantly mitigated damage both vivo models. Further NO-mediated prevalent early-onset Alzheimer's (AD) amyotrophic lateral sclerosis (ALS) regions not tumours. findings suggest critical other neurodegenerative disorders, providing targets therapeutic intervention.

Language: Английский

Citations

1
Multifactorial glial responses and their contributions to Alzheimer's disease continuum DOI Creative Commons
Masanori Hijioka, Tatsuya Manabe, Takashi Saito

et al.

Clinical and Experimental Neuroimmunology, Journal Year: 2023, Volume and Issue: 14(2), P. 82 - 91

Published: Feb. 10, 2023

Abstract Alzheimer's disease (AD) is the most common neurocognitive disorder. Various factors are intricately intertwined before clinical symptoms appear, although both amyloid‐β peptide deposition and neurofibrillary tangle formation (i.e. pathological hallmarks of AD brain) established. Among such factors, glial responses have been increasingly recognized as important roles in progression these pathologies viewed one component continuum. However, detailed molecular cellular mechanisms function underlying pathogenesis remain to be elucidated. Recent studies showed that peripheral immunity, gut microbiota or environmental influence brain pathophysiologies through communication with cells brain. This complexity makes understanding etiology difficult hinders development effective therapeutic strategies tackle this disease. Conversely, aged patients often suffer from multiple – not a single diseases multimorbidity, might related caused by other diseases. Hence, investigating systemic has become critical for identifying interventions. review aimed summarize current knowledge on research share perspectives functions regarding pathophysiology.

Language: Английский

Citations

2
Evidence for a role of human blood-borne factors in mediating age-associated changes in molecular circadian rhythms DOI Creative Commons
Jessica E. Schwarz,

Antonijo Mrčela,

Nicholas F. Lahens

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: July 18, 2023

Aging is associated with a number of physiologic changes including perturbed circadian rhythms; however, mechanisms by which rhythms are altered remain unknown. To test the idea that circulating factors mediate age-dependent in peripheral rhythms, we compared ability human serum from young and old individuals to synchronize culture. We collected blood apparently healthy (age 25–30) 70–76) at 14:00 used cultured fibroblasts. found sera equally competent initiating robust ~24 hr oscillations luciferase reporter driven clock gene promoter. However, cyclic expression affected, such promote cycling different sets genes. Genes lose rhythmicity entrainment oxidative phosphorylation Alzheimer’s Disease as identified STRING IPA analyses. Conversely, genes cholesterol biosynthesis increased cells entrained serum. involved cell cycle transcription/translation rhythmic both conditions. did not observe global difference distribution phase between groups, but peak several clock-controlled ( PER3, NR1D1, NR1D2, CRY1, CRY2, TEF ) lagged synchronized ex vivo Taken together, these findings demonstrate blood-borne affect have potential impact health disease via maintaining or disrupting respectively.

Language: Английский

Citations

2