Candesartan Neuroprotection in Rat Primary Neurons Negatively Correlates with Aging and Senescence: a Transcriptomic Analysis

AbstractPreclinical experiments and clinical trials demonstrated that angiotensin II AT1 receptor overactivity associates with aging and cellular senescence and that AT1 receptor blockers (ARBs) protect from age-related brain disorders. In a primary neuronal culture submitted to glutamate excitotoxicity, gene set enrichment analysis (GSEA) revealed expression of several hundred genes altered by glutamate and normalized by candesartan correlated with changes in expression in Alzheimer ’s patient’s hippocampus. To further establish whether our data correlated with gene expression alterations associated with aging and senescence, we compared our global transcriptional data with additional published datasets, including alterations in gene expression in the neocortex and cerebell um of old mice, human frontal cortex after age of 40, gene alterations in the Werner syndrome, rodent caloric restriction, Ras and oncogene-induced senescence in fibroblasts, and to tissues besides the brain such as the muscle and kidney. The most significant and enriched pathways associated with ag ing and senescence were positively correlated with alterations in gene expression in glutamate-injured neurons and, conversely, negatively correlated when the injured neurons were treated with candesartan. Our results involve multiple genes and pathways, including CAV1, CCND1, CDKN1A, CHEK1, ICAM1, IL-1B, IL-6, MAPK14, PTGS2, SERPINE1, and TP53, encoding proteins associated with aging and senescenc...
Source: Molecular Neurobiology - Category: Neurology Source Type: research

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Publication date: Available online 24 January 2020Source: The Lancet NeurologyAuthor(s): Shea J Andrews, Brian Fulton-Howard, Alison GoateSummaryBackgroundAlzheimer's disease is a debilitating and highly heritable neurological condition. As such, genetic studies have sought to understand the genetic architecture of Alzheimer's disease since the 1990s, with successively larger genome-wide association studies (GWAS) and meta-analyses. These studies started with a small sample size of 1086 individuals in 2007, which was able to identify only the APOE locus. In 2013, the International Genomics of Alzheimer's Project (IGAP) did...
Source: The Lancet Neurology - Category: Neurology Source Type: research
We examined whether Rhy promotes this regulation in bone marrow human mesenchymal stromal cells (BM-hMSCs). Results revealed (i) Rhy modulated biological activity by regulating the mitochondria, N-methyl-D-aspartate receptor subunit, and levels of FGFβ (basic fibroblast growth factor), BDNF (brain-derived neurotrophic factor), OXTR (oxytocin receptor) and ATP (Adenosine triphosphate); (ii) Rhy altered expression level of BM-MSC proliferation/differentiation-related transcription genes; and (iii) interestingly, Rhy amplified the glycolytic flow ratio and lactate dehydrogenase activity while reducing pyruvate dehydrogen...
Source: Cytotherapy - Category: Cytology Source Type: research
While most patients with Alzheimer's and Related Dementias (ADRD) prefer to die in nursing facilities, trends and factors associated with place of death for this population remain unknown.
Source: Journal of Pain and Symptom Management - Category: Palliative Care Authors: Source Type: research
CONCLUSIONS: Although our findings were inconclusive, the earlier age of onset observed among neurodegenerative disease patients carrying the CCR5-delta32 allele suggests that the deletion may have a detrimental effect in the context of neurodegeneration. PMID: 31972607 [PubMed - as supplied by publisher]
Source: Alzheimer Disease and Associated Disorders - Category: Psychiatry Tags: Alzheimer Dis Assoc Disord Source Type: research
Authors: Sun F, Chima E, Wharton T, Iyengar V Abstract Alzheimer's disease and related dementias (ADRD) affect over 50 million persons globally, and the number is expected to rise. In response, health ministries are developing and implementing policies and programs to systemically address the needs of individuals and families affected by ADRD. While national plans of action on ADRD are advancing among European Member States of World Health Organization (WHO), those in the Asia-Pacific and Americas are lagging behind. Since previous studies have largely ignored the Americas and Asia-Pacific-where approximately two-t...
Source: Pan American Journal of Public Health - Category: International Medicine & Public Health Tags: Rev Panam Salud Publica Source Type: research
Publication date: Available online 23 January 2020Source: SteroidsAuthor(s): Shimaa Saad El-Din, Laila Rashed, Engy Medhat, Basma Emad Aboulhoda, Ahmed Desoky Badawy, Asmaa Mohammed Shamseldeen, Marwa AbdelgwadAbstractBackgroundThe nuclear factor erythroid2-related factor2 (Nrf2), a chief transcriptional regulator of antioxidant response element (ARE), is considered a promising target for the prevention of Alzheimer’s disease (AD). Vitamin D has been recognized to have a crucial role in improving AD cognitive functions. The present study was conducted to evaluate the effects of active vitamin D analogue, Maxacalcitol...
Source: Steroids - Category: Drugs & Pharmacology Source Type: research
Publication date: April 2020Source: Biomedicine &Pharmacotherapy, Volume 124Author(s): Jin Qian, Mingqi Hou, Xian Wu, Chuanying Dai, Jiaqiang Sun, Liuyi DongAbstract2,3,5,4,-Tetrahydroxystilbene-2-O-β-d-glucoside (TSG) is the main active constituent of the traditional Chinese medicine, Polygonum multiflorum; it was discovered that the compound has various biological activities and medicinal value including anti-aging, antioxidative (via scavenging free radicals), antihypercholesterolemic, anti-atherosclerotic, anti-inflammatory, hepatoprotective, and anti-tumor effects. TSG aids in prevention and treatment of Alzh...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
Publication date: Available online 23 January 2020Source: NeuroscienceAuthor(s): Rajasekhar Reddy Chilakala, Aparna Lakshmi Manchikalapudi, Ashok Kumar, Aditya SunkariaAbstractMicroglia are the brain mononuclear phagocytes which plays a key role in neurodegenerative diseases, like Alzheimer's. Till date, microglia have been explored mostly for their neuro-inflammatory functions. Recent studies have shifted their focus towards less explored functions which involve non-autonomous clearance of protein aggregates. However, these functions are significantly affected by aging and neurodegeneration. In Alzheimer’s disease (...
Source: Neuroscience - Category: Neuroscience Source Type: research
AbstractMid-life hypertension and cerebrovascular dysfunction are associated with increased risk of later life dementia, including Alzheimer ’s disease (AD). The classical renin–angiotensin system (cRAS), a physiological regulator of blood pressure, functions independently within the brain and is overactive in AD. cRAS-targeting anti-hypertensive drugs are associated with reduced incidence of AD, delayed onset of cognitive decline, a nd reduced levels of Aβ and tau in both animal models and human pathological studies. cRAS activity is moderated by a downstream regulatory RAS pathway (rRAS), which is undera...
Source: Acta Neuropathologica - Category: Neurology Source Type: research
AIM: The clock drawing test (CDT) is widely used as a visual spatial ability test and screening test for dementia patients. The appearance frequency of qualitative errors obtained through the qualitative analysis of CDT may be related to the participant's ...
Source: SafetyLit - Category: International Medicine & Public Health Tags: Age: Elder Adults Source Type: news
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