Shaping the Nrf2-ARE-related pathways in Alzheimer's and Parkinson's diseases.

Shaping the Nrf2-ARE-related pathways in Alzheimer's and Parkinson's diseases. Ageing Res Rev. 2019 Aug 12;:100942 Authors: Fão L, Mota SI, Rego AC Abstract A failure in redox homeostasis is a common hallmark of Alzheimer's Disease (AD) and Parkinson's Disease (PD), two age-dependent neurodegenerative disorders (NDD), causing increased oxidative stress, oxidized/damaged biomolecules, altered neuronal function and consequent cell death. Activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a redox-regulated transcription factor, results in upregulation of cytoprotective and antioxidant enzymes/proteins, protecting against oxidative stress. Nrf2 regulation is achieved by various proteins and pathways, at both cytoplasmatic and nuclear level; however, the elaborate network of mechanisms involved in Nrf2 regulation may restrain Nrf2 pathway normal activity. Indeed, altered Nrf2 activity is involved in aging and NDD, such as AD and PD. Therefore, understanding the diversity of Nrf2 control mechanisms and regulatory proteins is of high interest, since more effective NDD therapeutics can be identified. In this review, we first introduce Keap1-Nrf2-ARE structure, function and regulation, with a special focus on the several pathways involved in Nrf2 positive and negative modulation, namely p62, PKC, PI3K/Akt/GSK-3β, NF-kB and p38 MAPK. We then briefly describe the evidences for oxidative stress and Nrf2 pathway deregulation in different st...
Source: Ageing Research Reviews - Category: Genetics & Stem Cells Authors: Tags: Ageing Res Rev Source Type: research

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Abstract As the global population ages, the incidence of neurodegenerative diseases has risen. Furthermore, it has been suggested that depression, especially in elderly people, may also be an indication of latent neurodegeneration. Stroke, Alzheimer's disease (AD), and Parkinson's disease (PD) are usually accompanied by depression. The urgent challenge is further enforced by psychiatric comorbid conditions, particularly the feeling of despair in these patients. Fortunately, as our understanding of the neurobiological substrates of maladies affecting the central nervous system (CNS) has increased, more therapeutic ...
Source: Neural Plasticity - Category: Neurology Authors: Tags: Neural Plast Source Type: research
Cho Kim Kim Given the difficulties of obtaining diseased cells, differentiation of neurons from patient-specific human induced pluripotent stem cells (iPSCs) with neural progenitor cells (NPCs) as intermediate precursors is of great interest. While cellular and transcriptomic changes during the differentiation process have been tracked, little attention has been given to examining spatial re-organization, which has been revealed to control gene regulation in various cells. To address the regulatory mechanism by 3D chromatin structure during neuronal differentiation, we examined the changes that take place during...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research
AbstractThe Nucleus Basalis of Meynert (NBM) is the main source of cholinergic neurons in the basal forebrain to be crucially involved in cognitive functions and whose degeneration correlates with cognitive decline in major degenerative pathologies as Alzheimer's and Parkinson ’s diseases. However, knowledge concerning NBM neurons derived from human brain is very limited to date.We recently characterized a primary culture of proliferating neuroblasts isolated from the human fetal NBM (hfNBM) as immature cholinergic neurons expressing the machinery to synthetize and release acetylcholine. Here we studied in detail ele...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research
Conclusions 18F-PI-2620 PET might be a sensitive tool to detect cortical tau deposits in patients with Aβ+ AD and Aβ+ non-AD tauopathies. Furthermore, this study showed that “off-target” binding in the basal ganglia does not affect 18F-PI-2620.
Source: Clinical Nuclear Medicine - Category: Nuclear Medicine Tags: Original Articles Source Type: research
(Lancaster University) After examining the brainstems of 186 young Mexico City residents aged between 11 months and 27 years of age, researchers, including Professor Barbara Maher from Lancaster University, found markers not only of Alzheimer's disease, but also of Parkinson's and of motor neurone disease (MND) too.These markers of disease were coupled with the presence of tiny, distinctive nanoparticles within the brainstem - their appearance and composition indicating they were likely to come from vehicle pollution.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
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: 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
Conclusions. Compound 14b exhibited high affinity and excellent subtype selectivity, which was then evaluated by in vitro autoradiography and in vivo PET imaging study after labeling with carbon-11. Ligand [11C]14b, which we named [11C]MG2-1904, demonstrated high brain uptake and excellent in vitro/in vivo specific binding towards mGlu2 with high metabolic stability in the brain. As proof-of-concept, our preliminary work demonstrated a successful example of visualizing mGlu2 in vivo derived from NAMs, which represents a promising chemotype for further development and optimization aimed for clinical translation.
Source: Theranostics - Category: Molecular Biology Authors: Tags: Research Paper Source Type: research
Dementia is a rapidly rising global health crisis that silently disables families and ends lives and livelihoods around the world. To date, however, no early biomarkers or effective therapies exist. It is now clear that brain microglia are more than mere bystanders or amyloid phagocytes; they can act as governors of neuronal function and homeostasis in the adult brain. Here, we highlight the fundamental role of microglia as tissue-resident macrophages in neuronal health. Then, we suggest how chronic impairment in microglia-neuron cross-talk may secure the permanence of the failure of synaptic and neuronal function and heal...
Source: ScienceNOW - Category: Science Authors: Tags: Neuroscience special/review Source Type: news
Abstract Misfolded and natively disordered globular proteins tend to aggregate together in an interwoven fashion to form fibrous, proteinaceous deposits referred to as amyloid fibrils. Formation and deposition of such insoluble fibrils are the characteristic features of a broad group of diseases, known as amyloidosis. Some of these proteins are known to cause several degenerative disorders in humans, such as Amyloid-Beta (Aβ) in Alzheimer's disease (AD), human Islet Amyloid Polypeptide (hIAPP, amylin) in type 2 diabetes, α-synuclein (α-syn) in Parkinson's disease (PD) and so on. The fact that thes...
Source: Archives of Biochemistry and Biophysics - Category: Biochemistry Authors: Tags: Arch Biochem Biophys Source Type: research
CONCLUSIONS: We did not observe clear associations between overall ambient PM2.5 concentrations or source apportioned ambient PM2.5 contributions and rates of neurologic disease hospitalizations. PMID: 33010415 [PubMed - as supplied by publisher]
Source: Annals of Epidemiology - Category: Epidemiology Authors: Tags: Ann Epidemiol Source Type: research
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