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lithium and Alzheimer's

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https://www.readbyqxmd.com/read/28253260/direct-keap1-nrf2-disruption-as-a-potential-therapeutic-target-for-alzheimer-s-disease
#1
Fiona Kerr, Oyinkan Sofola-Adesakin, Dobril K Ivanov, Jemma Gatliff, Beatriz Gomez Perez-Nievas, Hélène C Bertrand, Pedro Martinez, Rebecca Callard, Inge Snoeren, Helena M Cochemé, Jennifer Adcott, Mobina Khericha, Jorge Iván Castillo-Quan, Geoffrey Wells, Wendy Noble, Janet Thornton, Linda Partridge
Nrf2, a transcriptional activator of cell protection genes, is an attractive therapeutic target for the prevention of neurodegenerative diseases, including Alzheimer's disease (AD). Current Nrf2 activators, however, may exert toxicity and pathway over-activation can induce detrimental effects. An understanding of the mechanisms mediating Nrf2 inhibition in neurodegenerative conditions may therefore direct the design of drugs targeted for the prevention of these diseases with minimal side-effects. Our study provides the first in vivo evidence that specific inhibition of Keap1, a negative regulator of Nrf2, can prevent neuronal toxicity in response to the AD-initiating Aβ42 peptide, in correlation with Nrf2 activation...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28222508/chronic-lithium-treatment-in-a-rat-model-of-basal-forebrain-cholinergic-depletion-effects-on-memory-impairment-and-neurodegeneration
#2
Francesca Gelfo, Debora Cutuli, Annalisa Nobili, Paola De Bartolo, Marcello D'Amelio, Laura Petrosini, Carlo Caltagirone
Alzheimer's disease (AD) is an age-related neurodegenerative disorder with multifactorial etiopathogenesis, characterized by progressive loss of memory and other cognitive functions. A fundamental neuropathological feature of AD is the early and severe brain cholinergic neurodegeneration. Lithium is a monovalent cation classically utilized in the treatment of mood disorders, but recent evidence also advances a beneficial potentiality of this compound in neurodegeneration. Interestingly, lithium acts on several processes whose alterations characterize the brain cholinergic impairment at short and long term...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28123400/six-psychotropics-for-pre-symptomatic-early-alzheimer-s-mci-parkinson-s-and-huntington-s-disease-modification
#3
REVIEW
Edward C Lauterbach
The quest for neuroprotective drugs to slow the progression of neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD), has been largely unrewarding. Preclinical evidence suggests that repurposing quetiapine, lithium, valproate, fluoxetine, donepezil, and memantine for early and pre-symptomatic disease-modification in NDDs may be promising and can spare regulatory barriers. The literature of these psychotropics in early stage and pre-symptomatic AD, PD, and HD is reviewed and propitious findings follow...
November 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28093288/assessing-the-impact-of-lithium-chloride-on-the-expression-of-p-glycoprotein-at-the-blood-brain-barrier
#4
Stephanie A Newman, Yijun Pan, Jennifer L Short, Joseph A Nicolazzo
In addition to extruding drugs from the brain, P-glycoprotein (P-gp) at the blood-brain barrier (BBB) facilitates the brain-to-blood clearance of beta-amyloid (Aβ) and is down-regulated in Alzheimer's disease. Studies suggest that the mood-stabilizing drug lithium exerts a protective effect against Alzheimer's disease. Although the mechanisms underlying this effect are not fully understood, evidence suggests that lithium chloride (LiCl) increases P-gp expression in vitro, albeit at concentrations substantially outside the therapeutic window...
January 16, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28077724/trem2-promotes-microglial-survival-by-activating-wnt-%C3%AE-catenin-pathway
#5
Honghua Zheng, Lin Jia, Chia-Chen Liu, Zhouyi Rong, Li Zhong, Longyu Yang, Xiao-Fen Chen, John D Fryer, Xin Wang, Yun-Wu Zhang, Huaxi Xu, Guojun Bu
Triggering Receptor Expressed on Myeloid cells 2 (TREM2), which is expressed on myeloid cells including microglia in the CNS, has recently been identified as a risk factor for Alzheimer's disease (AD). TREM2 transmits intracellular signals through its transmembrane binding partner DNAX-activating protein 12 (DAP12). Homozygous mutations inactivating TREM2 or DAP12 lead to Nasu-Hakola disease; however, how AD risk-conferring variants increase AD risk is not clear. To elucidate the signaling pathways underlying reduced TREM2 expression or loss of function in microglia, we respectively knocked down and knocked out the expression of TREM2 in in vitro and in vivo models...
February 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28002662/association-between-lithium-use-and-risk-of-alzheimer-s-disease
#6
Chin Cheng, Peter Zandi, Elizabeth Stuart, Ching-Heng Lin, Pei-Yu Su, G Caleb Alexander, Tsuo-Hung Lan
OBJECTIVE: Current evidence for the association between use of lithium and risk of dementia is mixed. The objective of this study was to assess the risk of Alzheimer's disease associated with use of lithium. METHODS: A population-based, nested case-control study was conducted using data from the National Health Insurance Research Database in 2002 covering 24.5 million beneficiaries of the Taiwan National Health Insurance Program from January 1, 1997, to December 31, 2009...
February 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/27999295/special-issue-molecules-against-alzheimer
#7
EDITORIAL
Michael Decker, Diego Muñoz-Torrero
This Special Issue, entitled "Molecules against Alzheimer", gathers a number of original articles, short communications, and review articles on recent research efforts toward the development of novel drug candidates, diagnostic agents and therapeutic approaches for Alzheimer's disease (AD), the most prevalent neurodegenerative disorder and a leading cause of death worldwide. This Special Issue contains many interesting examples describing the design, synthesis, and pharmacological profiling of novel compounds that hit one or several key biological targets, such as cholinesterases, β-amyloid formation or aggregation, monoamine oxidase B, oxidative stress, biometal dyshomeostasis, mitochondrial dysfunction, serotonin and/or melatonin systems, the Wnt/β-catenin pathway, sigma receptors, nicotinamide phosphoribosyltransferase, or nuclear erythroid 2-related factor...
December 16, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27832289/glycogen-synthase-kinase-3%C3%AE-regulates-fractalkine-production-by-altering-its-trafficking-from-golgi-to-plasma-membrane-implications-for-alzheimer-s-disease
#8
Almudena Fuster-Matanzo, Jerónimo Jurado-Arjona, Stefano Benvegnù, Esther García, Patricia Martín-Maestro, Raquel Gómez-Sintes, Félix Hernández, Jesús Ávila
Glycogen synthase kinase-3β (GSK-3β) is a serine-threonine kinase implicated in multiple processes and signaling pathways. Its dysregulation is associated with different pathological conditions including Alzheimer's disease (AD). Here we demonstrate how changes in GSK-3β activity and/or levels regulate the production and subsequent secretion of fractalkine, a chemokine involved in the immune response that has been linked to AD and to other different neurological disorders. Treatment of primary cultured neurons with GSK-3β inhibitors such as lithium and AR-A014418 decreased full-length fractalkine in total cell extracts...
March 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27819842/low-dose-lithium-treatment-for-agitation-and-psychosis-in-alzheimer-disease-and-frontotemporal-dementia-a-case-series
#9
Davangere P Devanand, Gregory H Pelton, Kristina D'Antonio, Jesse G Strickler, William C Kreisl, James Noble, Karen Marder, Anne Skomorowsky, Edward D Huey
No abstract text is available yet for this article.
January 2017: Alzheimer Disease and Associated Disorders
https://www.readbyqxmd.com/read/27777112/stereological-investigation-of-the-ca1-pyramidal-cell-layer-in-untreated-and-lithium-treated-3xtg-ad-and-wild-type-mice
#10
Evelin L Schaeffer, Sergio Catanozi, Mark J West, Wagner F Gattaz
Pyramidal neuron loss in the hippocampal CA1 region is a very early hallmark of Alzheimer disease (AD). Lithium might be a therapeutic strategy for AD due to its neuroprotective and neurotrophic properties. This study used modern stereological techniques to investigate possible CA1 pyramidal neuron loss in 11-month-old triple transgenic AD (3xTg-AD) mice, and also the effects of therapeutic and subtherapeutic lithium doses on the number and density of CA1 pyramidal neurons and volume of CA1 pyramidal layer in 3xTg-AD and wild-type mice treated from 3 to 11 months of age...
January 2017: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/27490211/tideglusib-induces-apoptosis-in-human-neuroblastoma-imr32-cells-provoking-sub-g0-g1-accumulation-and-ros-generation
#11
Theodore Lemuel Mathuram, Vilwanathan Ravikumar, Lisa M Reece, Selvaraju Karthik, Changam Sheela Sasikumar, Kotturathu Mammen Cherian
Neuroblastoma is the most common tumor amongst children amounting to nearly 15% of cancer deaths. This cancer is peculiar in its characteristics, exhibiting differentiation, maturation and metastatic transformation leading to poor prognosis and low survival rates among children. Chemotherapy, though toxic to normal cells, has shown to improve the survival of the patient with emphasis given more towards targeting angiogenesis. Recently, Tideglusib was designed as an 'Orphan Drug' to target the neurodegenerative Alzheimer's disease and gained significant momentum in its function during clinical trials...
September 2016: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/27488422/lithium-restores-age-related-olfactory-impairment-in-the-ts65dn-mouse-model-of-down-syndrome
#12
Sandra Guidi, Patrizia Bianchi, Fiorenza Stagni, Andrea Giacomini, Marco Emili, Stefania Trazzi, Elisabetta Ciani, Renata Bartesaghi
In this review we look at this biological overlaps of neurodegenerative and psychiatric conditions, as exemplified by major depressive disorder (MDD). Recent work has highlighted how immune-inflammatory processes and their interactions with oxidative and nitrosative stress (O&NS), couple to drive changes in neuroregulatory tryptophan catabolite (TRYCAT), with consequences for serotonin availability for the melatonergic pathways. Such work significantly questions the validity and utility of non-biologically based current classification systems for psychiatric and neurodegenerative conditions...
August 1, 2016: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/27408673/lithium-to-the-rescue
#13
Richard S Jope, Charles B Nemeroff
Lithium, an element that Mother Nature has put in some drinking water sources, has been used for its curative powers for centuries. Today, it's given in capsule form as a mood stabilizer for bipolar disorder and depression. New research, however, reveals its role as a neuroprotector, and suggests that a better understanding of the role enzymes modulated by lithium play could lead to new treatments for Alzheimer's disease, Parkinson's disease, multiple sclerosis, and other neurodegenerative disorders.
January 2016: Cerebrum: the Dana Forum on Brain Science
https://www.readbyqxmd.com/read/27400857/lithium-suppression-of-tau-induces-brain-iron-accumulation-and-neurodegeneration
#14
P Lei, S Ayton, A T Appukuttan, S Moon, J A Duce, I Volitakis, R Cherny, S J Wood, M Greenough, G Berger, C Pantelis, P McGorry, A Yung, D I Finkelstein, A I Bush
Lithium is a first-line therapy for bipolar affective disorder. However, various adverse effects, including a Parkinson-like hand tremor, often limit its use. The understanding of the neurobiological basis of these side effects is still very limited. Nigral iron elevation is also a feature of Parkinsonian degeneration that may be related to soluble tau reduction. We found that magnetic resonance imaging T2 relaxation time changes in subjects commenced on lithium therapy were consistent with iron elevation. In mice, lithium treatment lowers brain tau levels and increases nigral and cortical iron elevation that is closely associated with neurodegeneration, cognitive loss and parkinsonian features...
March 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/27180786/the-impact-of-chronic-glycogen-synthase-kinase-3-inhibition-on-remodeling-of-normal-and-pre-diabetic-rat-hearts
#15
B Huisamen, T Lubelwana Hafver, D Lumkwana, A Lochner
PURPOSE: There is an ongoing search for new drugs and drug targets to treat diseases like Alzheimer's disease, cancer and type 2 diabetes (T2D). Both obesity and T2D are characterized by the development of a cardiomyopathy associated with increased hypertension and compensatory left ventricular hypertrophy. Small, specific glycogen synthase kinase-3 (GSK-3) inhibitors were developed to replace lithium chloride for use in psychiatric disorders. In addition, they were advocated as treatment for T2D since GSK-3 inhibition improves blood glucose handling...
June 2016: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/27150910/alkali-metals-levels-in-the-human-brain-tissue-anatomical-region-differences-and-age-related-changes
#16
Patrícia Ramos, Agostinho Santos, Edgar Pinto, Nair Rosas Pinto, Ricardo Mendes, Teresa Magalhães, Agostinho Almeida
The link between trace elements imbalances (both "toxic" and "essential") in the human brain and neurodegenerative disease has been subject of extensive research. More recently, some studies have highlighted the potential role of the homeostasis deregulation of alkali metals in specific brain regions as key factor in the pathogenesis of neurodegenerative diseases such as multiple sclerosis and Alzheimer's disease. Using flame atomic emission spectrometry and inductively coupled plasma-mass spectrometry after microwave-assisted acid digestion of the samples, alkali metals (Na, K, Li, Rb and Cs) were determined in 14 different areas of the human brain (frontal cortex, superior and middle temporal gyri, caudate nucleus, putamen, globus pallidus, cingulated gyrus, hippocampus, inferior parietal lobule, visual cortex of the occipital lobe, midbrain, pons, medulla and cerebellum) of adult individuals (n=42; 71±12, range: 50-101 years old) with no known history and evidence of neurodegenerative, neurological or psychiatric disorder...
December 2016: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/27137221/pharmacological-management-of-agitation-and-aggression-in-alzheimer-s-disease-a-review-of-current-and-novel-treatments
#17
REVIEW
Celina S Liu, Myuri Ruthirakuhan, Sarah A Chau, Nathan Herrmann, André F Carvalho, Krista L Lanctôt
Agitation and aggression are common neuropsychiatric symptoms of Alzheimer's disease and are highly prevalent in people with dementia. When pharmacological intervention becomes necessary, current clinical practice guidelines recommend antipsychotics, cholinesterase inhibitors, and some antidepressants. However, those interventions have modest to low efficacy, and those with the highest demonstrated efficacy have significant safety concerns. As a result, current research is focusing on novel compounds that have different mechanisms of action and that may have a better balance of efficacy over safety...
2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27073741/repurposing-psychiatric-medicines-to-target-activated-microglia-in-anxious-mild-cognitive-impairment-and-early-parkinson-s-disease
#18
REVIEW
Edward C Lauterbach
Anxiety is common in the Mild Cognitive Impairment (MCI) stage of Alzheimer's disease (AD) and the pre-motor stages of Parkinson's disease (PD). A concomitant and possible cause of this anxiety is microglial activation, also considered a key promoter of neurodegeneration in MCI and early PD via inflammatory mechanisms and the generation of degenerative proinflammatory cytokines. Psychiatric disorders, prevalent in AD and PD, are often treated with psychiatric drugs (psychotropics), raising the question of whether psychotropics might therapeutically affect microglial activation, MCI, and PD...
2016: American Journal of Neurodegenerative Disease
https://www.readbyqxmd.com/read/26979735/inhibition-of-glycogen-synthase-kinase-3-an-emerging-target-in-the-treatment-of-traumatic-brain-injury
#19
Seong S Shim, Grace E Stutzmann
Although traumatic brain injury (TBI) has been a major public health concern for decades, the pathophysiological mechanism of TBI is not clearly understood, and an effective medical treatment of TBI is not available at present. Of particular concern is sustained TBI, which has a strong tendency to take a deteriorating neurodegenerative course into chronic traumatic encephalopathy (CTE) and dementia, including Alzheimer's disease. Tauopathy and beta amyloid (Aβ) plaques are known to be the key pathological markers of TBI, which contribute to the progressive deterioration associated with TBI such as CTE and Alzheimer's disease...
December 1, 2016: Journal of Neurotrauma
https://www.readbyqxmd.com/read/26892289/lithium-a-therapy-for-ad-current-evidence-from-clinical-trials-of-neurodegenerative-disorders
#20
Orestes V Forlenza, Ivan Aprahamian, Vanessa J de Paula, Tomas Hajek
BACKGROUND: Preclinical studies have shown that lithium modifies pathological cascades implicated in certain neurodegenerative disorders, such as Alzheimer's disease (AD), Huntigton`s disease (HD), multiple system atrophy (MSA) and amyotrophic lateral sclerosis (ALS). A critical question is whether these pharmacodynamic properties of lithium translate into neurodegenerative diseases modifying effects in human subjects. METHODS: We reviewed all English controlled clinical trials published in PubMed, PsycINFO, Embase, SCOPUS, ISI-Web with the use of lithium for the treatment of neurodegenerative disorders between July 2004 and July 2014...
2016: Current Alzheimer Research
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