The evolution of karyotypically stabilized short-lived (SL) and long-lived (LL) cytoraces in the laboratory have been established and validated through our previous lifespan studies. In the present investigation, we examined the possible reason(s) for the differential longevity among selected members of SL and LL cytoraces, employing the well known paraquat (PQ) resistance bioassay. Exposure of these races to varying concentrations of PQ revealed relatively higher resistance among LL cytoraces than SL cytoraces, as evident by the lower incidence of mortality. Biochemical analysis for endogenous markers of oxidative stress revealed that LL-2 cytorace exhibited lower reactive oxygen species (ROS) and lipid peroxidation (LPO) levels, higher activity levels of superoxide dismutase (SOD), and coupled with higher levels of reduced glutathione (GSH) compared with the levels found in SL-2 cytorace. These findings suggest that the higher susceptibility of SL cytoraces to PQ challenge may be, at least in part, related to the higher endogenous levels of oxidative stress markers. Although the precise mechanisms responsible for the longer longevity among LL cytoraces of the nasuta-albomicans complex of Drosophila merits further investigation, our data suggest that the relatively longer lifespan may be related to the status of endogenous markers that renders them more resistant towards oxidative-stress-mediated lethality, as evident in the PQ assay.
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http://dx.doi.org/10.1139/g11-049 | DOI Listing |
Background: Senile dementia (SD) is a deteriorative organic brain disorder and it comprises Alzheimer's disease (AD) as a major variant. SD is shown impairment of mental capacities whereas AD is degeneration of neurons. According to World Health Organization (WHO) report; more than 55 million peoples have dementia and it is raising 10 million new cases every year.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
The University of Texas Health Science Center at Houston, Houston, TX, USA.
Background: Developing drugs for treating Alzheimer's disease (AD) has been extremely challenging and costly due to limited knowledge on underlying biological mechanisms and therapeutic targets. Repurposing drugs or their combination has shown potential in accelerating drug development due to the reduced drug toxicity while targeting multiple pathologies.
Method: To address the challenge in AD drug development, we developed a multi-task machine learning pipeline to integrate a comprehensive knowledge graph on biological/pharmacological interactions and multi-level evidence on drug efficacy, to identify repurposable drugs and their combination candidates RESULT: Using the drug embedding from the heterogeneous graph representation model, we ranked drug candidates based on evidence from post-treatment transcriptomic patterns, mechanistic efficacy in preclinical models, population-based treatment effect, and Phase 2/3 clinical trials.
Alzheimers Dement
December 2024
School of Medical & Allied Sciences, K.R. Mangalam University, Gurugram, Haryana, India.
Background: Parkinson's disease is an hypokinetic disorder characterized by selective loss of dopaminergic in substantia nigra pars compacta (SNPc) region of mid-brain. Dopaminergic degeneration of neurons is considered to be due to oxidative stress, neuroinflammation, neurons mitochondrial dysfunction and glutamate excitotoxicity etc. Filgrastim has been reported to produce anti-oxidant, anti-inflammatory and neuromodulatory actions in previous studies.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Afe Babalola University, Ado-Ekiti (ABUAD), Ado-Ekiti, Ekiti state, Nigeria.
Background: The impact of probiotics as gut and immunological modulator in restoring gut microbial balance and immune cells expression have generated much attention in the health sector. Its inhibitory effect on bacterial translocation and associated neural inflammatory processes has been reported. However, there is scarcity of data on its neuroprotective impact against neuroinflammation-associated neurodegeneration and memory impairment.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Yonsei University, Incheon, Incheon, Korea, Republic of (South).
Background: Cyclin Y (CCNY) is a member of cyclin protein family inhibiting long-term synaptic plasticity, which is related to the learning and memory function in neuronal system. Recently, CCNY has been reported to associate with the cognitive deficits in Alzheimer's disease (AD).
Method: In this study, we discovered PFTAIRE peptide to diminish CCNY protein level and to ameliorate cognitive dysfunction in AD.
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