NVP-BEZ235 (Dactolisib) Has Protective Effects in a Transgenic Mouse Model of Alzheimer ’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disease and the main cause of dementia. Its major symptom is memory loss, which is a result of neuronal cell death, which is accompanied by neuroinflammation. Some studies indicate the overactivation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) pathway in this disease, being, thus, a potential target for pharmacological treatment. Here, we used a transgenic mouse model of AD that expresses a mutant amyloid-β precursor protein (T41 mice) to investigate the effects of dactolisib (alternative name: NVP-BEZ235, abbreviation BEZ), a dual PI3K/mTOR inhibitor. Ten-months-old T41 animals were treated for 14 days with BEZ or vehicle via oral gavage and then submitted to social memory, open field and contextual conditioned fear tests. Hippocampal slices were prepared and Aβ1-42 content, NeuN, Iba-1, CD68 and GFAP were evaluated. Tissues were further processed to evaluate cytokines levels through cytometric bead array. The treatment with BEZ (5 mg/kg) reduced social memory impairment in T41 mice. However, BEZ did not have any effect on altered Aβ levels, NeuN, or GFAP staining. The drug reduced the CD68/Iba-1 ratio in CA3 region of hippocampus. Finally, BEZ diminished IL-10 levels in T41 mice. Thus, although its mechanisms are not clear, BEZ protects against memory impairment, reduces microglial activation and reestablishes IL-10 levels, revealing beneficial ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research

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Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
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Source: Daily Express - Health - Category: Consumer Health News Source Type: news
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Source: Daily Express - Health - Category: Consumer Health News Source Type: news
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Source: Daily Express - Health - Category: Consumer Health News Source Type: news
AbstractThe concept of the right temporal variant of frontotemporal dementia (rtvFTD) is still equivocal. The syndrome accompanying predominant right anterior temporal atrophy has previously been described as memory loss, prosopagnosia, getting lost and behavioural changes. Accurate detection is challenging, as the clinical syndrome might be confused with either behavioural variant FTD (bvFTD) or Alzheimer ’s disease. Furthermore, based on neuroimaging features, the syndrome has been considered a right-sided variant of semantic variant primary progressive aphasia (svPPA). Therefore, we aimed to demarcate the clinical...
Source: Brain - Category: Neurology Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Daily Express - Health - Category: Consumer Health News Source Type: news
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Source: World of Psychology - Category: Psychiatry & Psychology Authors: Tags: Psychology Around the Net alzheimer's Body Dysmorphic Disorder Boundaries Codependency Eating Disorders Oxytocin Postpartum revenge bedtime procrastination Sleep Source Type: blogs
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Source: Daily Express - Health - Category: Consumer Health News Source Type: news
This study investigated the ability of amnesia to predict AD in a clinicopathological dementia series. Ninety-one patients to which free and cued verbal memory assessment was administered during early cognitive decline, were followed until autopsy. Patients' histological diagnoses were classified as pure AD, mixed AD, and non-AD pathologies. Data-driven automated classification procedures explored the correspondence between memory performance and pathological diagnoses. Classifications revealed 3 clusters of performance reflecting different levels of amnesia. Little correspondence between these clusters and the presence of...
Source: Neurobiology of Aging - Category: Geriatrics Authors: Tags: Neurobiol Aging Source Type: research
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