Pathological Progression Induced by the Frontotemporal Dementia-Associated R406W Tau Mutation in Patient-Derived iPSCs

In this study, we established patient-derived induced pluripotent stem cell (iPSC) models to investigate the disease pathology induced by the R406W mutation. We generated iPSCs from patients and established isogenic lines using CRISPR/Cas9. The iPSCs were induced into cerebral organoids, which were dissociated into cortical neurons with high purity. In this neuronal culture, the mutant tau protein exhibited reduced phosphorylation levels and was increasingly fragmented by calpain. Furthermore, the mutant tau protein was mislocalized and the axons of the patient-derived neurons displayed morphological and functional abnormalities, which were rescued by microtubule stabilization. The findings of our study provide mechanistic insight into tau pathology and a potential for therapeutic intervention.Graphical Abstract
Source: Stem Cell Reports - Category: Stem Cells Source Type: research

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In this study, we established a human neuronal culture system using induced pluripotent stem cells (iPSCs) to evaluate the possible effects of natural compounds on the amyloid phenotype. Unexpectedly, we found that combinational treatment of carotenoids, but not docosahexaenoic acid, significantly decreased Aβ secretion from iPSC-derived human cortical neurons. Importantly, the effects of the carotenoids resulted from specific inhibition of BACE1 activity and not from expression changes in APP or BACE1. Therefore, these results indicate a novel beneficial function of carotenoids in the anti-amyloidogenic processing of...
Source: Neuroscience Research - Category: Neuroscience Source Type: research
Authors: Sun L, Li M, Sun X, Li X Abstract INTRODUCTION: Present investigation determines the effect of zerumbone on the proliferation of stem cells in vascular dementia (VD) rats. MATERIAL AND METHODS: Vascular dementia was induced by cerebral ischemia and reperfusion through non-invasive clamp. Rats were treated with zerumbone 50 mg/kg and 100 mg/kg intraperitoneally 30 min for four weeks after the surgery. Cognitive functions are determined by the Morris water maze (MWM) test and neurological function score in VD rats. Moreover mediators of inflammation and parameters of oxidative stress were estimated in th...
Source: Folia Neuropathologica - Category: Neurology Tags: Folia Neuropathol Source Type: research
Publication date: Available online 18 September 2019Source: NeuronAuthor(s): Peter Dongmin Sohn, Cindy Tzu-Ling Huang, Rui Yan, Li Fan, Tara E. Tracy, Carolina M. Camargo, Kelly M. Montgomery, Taylor Arhar, Sue-Ann Mok, Rebecca Freilich, Justin Baik, Manni He, Shiaoching Gong, Erik D. Roberson, Celeste M. Karch, Jason E. Gestwicki, Ke Xu, Kenneth S. Kosik, Li GanSummaryDysregulation of neuronal excitability underlies the pathogenesis of tauopathies, including frontotemporal dementia (FTD) with tau inclusions. A majority of FTD-causing tau mutations are located in the microtubule-binding domain, but how these mutations alte...
Source: Neuron - Category: Neuroscience Source Type: research
In this study, researchers studied 438,952 participants in the UK Biobank, who had a total of 24,980 major coronary events - defined as the first occurrence of non-fatal heart attack, ischaemic stroke, or death due to coronary heart disease. They used an approach called Mendelian randomisation, which uses naturally occurring genetic differences to randomly divide the participants into groups, mimicking the effects of running a clinical trial. People with genes associated with lower blood pressure, lower LDL cholesterol, and a combination of both were put into different groups, and compared against those without thes...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
We report the generation and characterization of an induced pluripotent stem cell (iPSC) line derived from a female PD patient carrying the L444P/wt mutation. The iPSC line presented a normal morphology, expressed endogenous pluripotency markers, could be differentiated into endodermal, mesodermal and ectodermal cells, was free from Sendai vectors and reprogramming factors, had a normal karyotype and maintained the original GBA1 genotype. Thus, this iPSC line can serve to establish cellular models of PD.
Source: Stem Cell Research - Category: Stem Cells Source Type: research
We examined human lung tissue from COPD patients and normal control subjects, and found a substantial increase in p16-expressing alveolar cells in COPD patients. Using a transgenic mouse deficient for p16, we demonstrated that lungs of mice lacking p16 were structurally and functionally resistant to CS-induced emphysema due to activation of IGF1/Akt regenerative and protective signaling. Fat Tissue Surrounds Skeletal Muscle to Accelerate Atrophy in Aging and Obesity https://www.fightaging.org/archives/2019/09/fat-tissue-surrounds-skeletal-muscle-to-accelerate-atrophy-in-aging-and-obesity/ Researchers her...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Fifteen years later, neurologist Dr. S. Thomas Carmichael can still recall the patient who sparked his determination to find a cure for vascular dementia.“She was a 55-year-old investment banker who couldn’t keep up with her spreadsheets and daily intellectual demands,” said Carmichael, co-director of theEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. “As it turned out, she had vascular dementia. I found it just remarkable that there wasn’t anything we could do to help her get better. I’ve been studying the disease ever since.”Unfortunately for ...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
In conclusion, in the absence of obesity, visceral adipose tissue possesses a pronounced anti-inflammatory phenotype during aging which is further enhanced by exercise. Methods of Inducing Cellular Damage are Rarely Relevant to Aging, and the Details Matter https://www.fightaging.org/archives/2019/08/methods-of-inducing-cellular-damage-are-rarely-relevant-to-aging-and-the-details-matter/ One of the major challenges in aging research is determining whether or not models of cellular or organismal damage and its consequences are in any way relevant to the natural processes of aging. One can hit a brick with...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Stem cells are not FDA-approved for joint pain, cataracts, depression, autism, dementia, or heart disease, but stem cell clinics around the country are offering treatment for these very conditions.Medscape
Source: Medscape Today Headlines - Category: Consumer Health News Tags: Internal Medicine Commentary Source Type: news
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