Is α-synuclein, Like Tau, Driven to Aggregate by the Activities of Inflammatory Microglia?

What are the important steps in the progression of neurodegenerative diseases characterized by the presence of protein aggregates? These aggregates are misfolded or otherwise altered proteins that precipitate to form solid deposits. This means α-synuclein in the case of Parkinson's disease, or amyloid-β and tau in the cause of Alzheimer's disease, to pick the best known examples. A growing body of evidence is pointing to dysfunction and inflammation in the immune cells known as microglia, a type of macrophage resident in the central nervous system. Like macrophages elsewhere in the body, microglia are responsible for chasing down pathogens and clearing up debris. They also participate in a range of other supporting activities that assist the function of neurons. In Alzheimer's disease, there is compelling evidence for microglia to be driven into an inflammatory state by the presence of amyloid-β. They act as the bridge between the mild earlier stage of the condition, in which amyloid-β accumulates, and the later stage in which tau aggregates form and neurons die. It is the chronic inflammation and dysfunction of microglia in brain tissue that drives this more severe tau pathology. Inflammatory behavior in microglia appears to involve significant numbers of senescent microglia, and researchers have shown that removing these senescent cells can turn back tau pathology in mouse models and reduce levels of neuroinflammation. Lingering senescent cells o...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs

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Publication date: Available online 15 October 2019Source: Life SciencesAuthor(s): He Li, Yin Luo, Luojiang Zhu, Weilong Hua, Yongxin Zhang, Hongjian Zhang, Lei Zhang, Zifu Li, Pengfei Xing, Yongwei Zhang, Bo Hong, Pengfei Yang, Jianmin LiuAbstractGlia is an important component of the nervous system that is involved in neurotransmitter uptake, signal transduction, myelin synthesis, neurodevelopment, and immune response. Exosomes are extracellular vesicles that are secreted from certain types of cells, and are known to mediate glia function. Glia-derived exosomes (GDEs) can transport proteins, nucleotides and cellular waste,...
Source: Life Sciences - Category: Biology Source Type: research
This study investigated the possibility of significant interactions between these molecules that are involved in the late‐stage of Alzheimer's disease (AD), Parkinson disease (PD), Parkinson disease dementia (PDD), dementia with Lewy bodies (DLB), and controls using ELISA assays, aut oradiography, and mRNA in situ hybridization assay. Interestingly, lower DNA/RNA oxidative adducts levels in the caudate and putamen of diseased brains were observed with the exception of an increased DNA oxidative product in the caudate of AD brains. Similar changes were found for dopamine concentr ation and vesicular monoamine transporter ...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research
In conclusion, a polypharmacology approach of combining established, prolongevity drug inhibitors of specific nodes may be the most effective way to target the nutrient-sensing network to improve late-life health. Deletion of p38α in Neurons Slows Neural Stem Cell Decline and Loss of Cognitive Function in Mice https://www.fightaging.org/archives/2019/10/deletion-of-p38%ce%b1-in-neurons-slows-neural-stem-cell-decline-and-loss-of-cognitive-function-in-mice/ Researchers here provide evidence for p38α to be involved in the regulation of diminished neural stem cell activity with age. It is thought...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Neuroinflammation is a condition characterized by the elaboration of proinflammatory mediators within the central nervous system. Neuroinflammation has emerged as a dominant theme in contemporary neuroscience due to its association with neurodegenerative disease states such as Alzheimer's disease, Parkinson's disease and Huntington's disease. While neuroinflammation often is associated with damage to the CNS, it also can occur in the absence of neurodegeneration, e.g., in association with systemic infection.
Source: Metabolism - Clinical and Experimental - Category: Biomedical Science Authors: Source Type: research
Traumatic brain injury (TBI) is a leading cause of death and disability, contributing to ~30% of all injury-related deaths in the US. TBI occurs when a force transmitted to the head causes neuropathologic damage and impairment of brain function. TBI doubles risk of suicide and is the major determinant of acquired seizure disorders. TBI arising from closed head trauma (CHT) significantly increases the risk of developing Alzheimer's disease (AD), Parkinson's disease (PD) and chronic traumatic encephalopathy (CTE).
Source: Metabolism - Clinical and Experimental - Category: Biomedical Science Authors: Source Type: research
Purpose of review Although ketogenic diet therapies (KDTs) were first developed as a treatment for patients with epilepsy, their potential efficacy for a broader number of neurologic and nonneurologic disorders and conditions has been explored over the last 10–20 years. The most recent clinical trials of KDTs in adults have highlighted common methodological aspects that can either facilitate or thwart appropriate risk/benefit analyses, comparisons across studies, and reproducibility of findings in future studies. Recent findings Recent evidence suggests that KDTs not only improve seizure control, but also improv...
Source: Current Opinion in Clinical Nutrition and Metabolic Care - Category: Nutrition Tags: NUTRITION AND PHYSIOLOGICAL FUNCTION: Edited by Labros S. Sidossis and Annemie M.W. Schols Source Type: research
Acetylcholine is a neurotransmitter that plays a key role in brain and muscle function. Here, we look at what acetylcholine does and describe medical conditions linked with it, including Alzheimer ’s and Parkinson’s, and their treatments.
Source: Parkinson's Disease News From Medical News Today - Category: Neurology Tags: Neurology / Neuroscience Source Type: news
Publication date: October 2019Source: Chinese Journal of Analytical Chemistry, Volume 47, Issue 10Author(s): Xin WANG, Ping LI, Wen ZHANG, Bo TANGAbstractBrain possesses a unique chemical composition and reactivity. Bioactive molecules in brains including metal ions, reactive oxygen species, neurotransmitters and neurotransmitter hydrolases play multifarious and pivotal roles in the function of brain. These molecules keep steady-state concentrations for maintaining the brain's structure and function. However, the abnormal changes in bioactive molecular levels are associated with various brain diseases such as Parkinson's d...
Source: Chinese Journal of Analytical Chemistry - Category: Chemistry Source Type: research
Abstract Deltamethrin (DM) is widely used in agriculture, veterinary medicine and control of domestic pests. Epidemiological studies suggest that DM exposure is a risk factor for neurodegenerative disorders such as Parkinson's (PD) and Alzheimer diseases; however the mechanisms are elusive. In the present study we evaluated the effects of intracerebroventricular (i.c.v.) administration of DM on locomotion activity, spatial working memory and dopaminergic pathway in the rat. Middle-aged male Wistar rats received three i.c.v. injections of DM 0.5 μg, DM 5 μg or vehicle, every other day. Across th...
Source: Brain Research Bulletin - Category: Neurology Authors: Tags: Brain Res Bull Source Type: research
The SENS Research Foundation should need no introduction to this audience, but, just in case, this is one of the few non-profit organizations dedicated to advancing the state of the art in rejuvenation research and development. The focus of the SENS Research Foundation staff is on unblocking lines of research that are presently moving too slowly, rather than on reinforcing success. The co-founder, Aubrey de Grey, assembled the Strategies for Engineered Negligible Senescence (SENS) going on twenty years ago. It was, and is, a synthesis of what is known in the research community regarding the root causes of aging. In the SEN...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
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