Is Alzheimer's disease an inflammasomopathy?

Is Alzheimer's disease an inflammasomopathy? Ageing Res Rev. 2019 Sep 29;:100966 Authors: Pereira CF, Santos AE, Moreira PI, Pereira AC, Sousa FJ, Cardoso SM, Cruz MT Abstract Alzheimer's disease (AD) is the most common form of dementia in the elderly and, despite the tremendous efforts researchers have put into AD research, there are no effective options for prevention and treatment of the disease. The best way to reach this goal is to clarify the mechanisms involved in the onset and progression of AD. In the last few years the views about the drivers of AD have been changing and nowadays it is believed that neuroinflammation takes center stage in disease pathogenesis. Herein, we provide an overview about the role of neuroinflammation in AD describing the role of microglia and astroglia is this process. Then, we will debate the NLRP3 inflammasome putting the focus on its activation through the canonical, non-canonical and alternative pathways and the triggers involved herein namely endoplasmic reticulum stress, mitochondrial dysfunction, reactive oxygen species and amyloid β peptide. Data supporting the hypothesis that inflammasome-mediated peripheral inflammation may contribute to AD pathology will be presented. Finally, a brief discussion about the therapeutic potential of NLRP3 inflammasome modulation is also provided. PMID: 31577960 [PubMed - as supplied by publisher]
Source: Ageing Research Reviews - Category: Genetics & Stem Cells Authors: Tags: Ageing Res Rev Source Type: research

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In this study, we found that older nematodes have higher ROS levels. Interestingly, after hydrogen treatment, the ROS levels were significantly decreased, and hydrogen could significantly extend the lifespans of the N2, sod-3 and sod-5 mutant strains, by approximately 22.7%, 9.5%, and 8.7%, respectively. In addition, aging is regulated by a variety of pathways, such as the insulin signaling pathway, the rapamycin target signaling pathway, and the caloric restriction pathway. However, our results showed that the lifespans of the daf-2 and daf-16 strains, in which these pathways are upregulated, were not affected afte...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract Population aging, as well as the handling of age-associated diseases, is a worldwide increasing concern. Among them, Alzheimer's disease stands out as the major cause of dementia culminating in full dependence on other people for basic functions. However, despite numerous efforts, in the last decades, there was no new approved therapeutic drug for the treatment of the disease. Calcium-activated potassium channels have emerged as a potential tool for neuronal protection by modulating intracellular calcium signaling. Their subcellular localization is determinant of their functional effects. When located on ...
Source: The International Journal of Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Int J Biochem Cell Biol Source Type: research
In conclusion, our study demonstrated that Nrf2 deficiency promoted the increasing trend of autophagy during aging in skeletal muscle. Nrf2 deficiency and increasing age may cause excessive autophagy in skeletal muscle, which can be a potential mechanism for the development of sarcopenia. To What Degree is Chondrocyte Hypertrophy in Osteoarthritis Due to Cellular Senescence? https://www.fightaging.org/archives/2020/04/to-what-degree-is-chondrocyte-hypertrophy-in-osteoarthritis-due-to-cellular-senescence/ Senescent cells are large. They do not replicate, that function is disabled, but it is as if they go ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
In conclusion, elevated brain amyloid was associated with family history and APOE ε4 allele but not with multiple other previously reported risk factors for AD. Elevated amyloid was associated with lower test performance results and increased reports of subtle recent declines in daily cognitive function. These results support the hypothesis that elevated amyloid represents an early stage in the Alzheimer's continuum. Blood Metabolites as a Marker of Frailty https://www.fightaging.org/archives/2020/04/blood-metabolites-as-a-marker-of-frailty/ Frailty in older people is usually diagnosed in a sympt...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: Harris LD, Jasem S, Licchesi JDF Abstract Alzheimer's disease (AD) is the most common form of dementia, most prevalent in the elderly population and has a significant impact on individuals and their family as well as the health care system and the economy. While the number of patients affected by various forms of dementia including AD is on the increase, there is currently no cure. Although genome-wide association studies have identified genetic markers for familial AD, the molecular mechanisms underlying the initiation and development of both familial and sporadic AD remain poorly understood. Most neurode...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
This study delves into the mechanisms by which a short period of fasting can accelerate wound healing. Fasting triggers many of the same cellular stress responses, such as upregulated autophagy, as occur during the practice of calorie restriction. It isn't exactly the same, however, so it is always worth asking whether any specific biochemistry observed in either case does in fact occur in both situations. In particular, the period of refeeding following fasting appears to have beneficial effects that are distinct from those that occur while food is restricted. Multiple forms of therapeutic fasting have been repor...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Authors: Khosravi S, Harner ME Abstract Mitochondria perform a plethora of functions in various cells of different tissues. Their architecture differs remarkably, for instance in neurons versus steroidogenic cells. Furthermore, aberrant mitochondrial architecture results in mitochondrial dysfunction. This indicates strongly that mitochondrial architecture and function are intimately linked. Therefore, a deep knowledge about the determinants of mitochondrial architecture and their function on a molecular level is of utmost importance. In the past decades, various proteins and protein complexes essential for formatio...
Source: Biological Chemistry - Category: Chemistry Tags: Biol Chem Source Type: research
Abstract Alzheimer's Disease (AD) therapeutics based on the amyloid hypothesis have repeatedly failed in clinical trials. Together with numerous reports that amyloid is present in brains from aged individuals without cognitive dysfunction, this suggests that the association of amyloid with AD is collateral rather than causal. The preeminence of the amyloid hypothesis has resulted in the 'systematic …thwart[ing of] alternative approaches' to AD/dementia driven by a 'cabal' of amyloid acolytes who have effectively controlled the ideas funded and published, which startups received venture investment and which ...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research
Authors: Chowdhury A, Rajkumar AP Abstract OBJECTIVES: Lewy body dementia (LBD) is the second most prevalent neurodegenerative dementia, and it causes more morbidity and mortality than Alzheimer's disease. Several genetic associations of LBD have been reported, and their functional implications remain uncertain. Hence, we aimed to do a systematic review of all gene expression studies that investigated people with LBD for improving our understanding of LBD molecular pathology and for facilitating discovery of novel biomarkers and therapeutic targets for LBD. METHODS: We systematically reviewed five online databa...
Source: Acta Neuropsychiatrica - Category: Psychiatry Tags: Acta Neuropsychiatr Source Type: research
We report a new class of natural-product-inspired covalent inhibitors of telomerase that target the catalytic active site. Age-Related Epigenetic Changes that Suppress Mitochondrial Function https://www.fightaging.org/archives/2020/03/age-related-epigenetic-changes-that-suppress-mitochondrial-function/ Today's open access research reports on two specific epigenetic changes observed in old individuals that act to reduce mitochondrial function. This joins an existing list of genes for which expression changes are known to impact mitochondrial function with age. A herd of hundreds of mitochondria are found ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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