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https://www.readbyqxmd.com/read/28214632/synthesis-of-new-heterocyclic-compounds-based-on-pyrazolopyridine-scaffold-and-evaluation-of-their-neuroprotective-potential-in-mpp-induced-neurodegeneration
#1
Jabrane Jouha, Mohammed Loubidi, Jamila Bouali, Salha Hamri, Abderrafia Hafid, Franck Suzenet, Gérald Guillaumet, Taner Dagcı, Mostafa Khouili, Fadime Aydın, Luciano Saso, Güliz Armagan
Neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and Huntington's disease affect millions of people in the world. Thus several new approaches to treat brain disorders are under development. The aim of the present study is to synthesize potential neuroprotective heterocyclic compounds based on pyrazolopyridine derivatives and then to evaluate their effects in MPP(+)-induced neurodegeneration in human neuroblastoma cell line (SH-SY5Y cells). The effects of the compounds on cell viability were measured by MTT assay and the changes in apoptosis-related proteins including bax, Bcl-2, Bcl-xl and caspase-3 were investigated by western blot technique...
February 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28213441/secreted-metalloproteinase-adamts-3-inactivates-reelin
#2
Himari Ogino, Arisa Hisanaga, Takao Kohno, Yuta Kondo, Kyoko Okumura, Takana Kamei, Tempei Sato, Hiroshi Asahara, Hitomi Tsuiji, Masaki Fukata, Mitsuharu Hattori
The secreted glycoprotein Reelin regulates embryonic brain development and adult brain functions. It has been suggested that reduced Reelin activity contributes to the pathogenesis of several neuropsychiatric and neurodegenerative disorders, such as schizophrenia and Alzheimer's disease; however, non-invasive methods that can upregulate Reelin activity in vivo have yet to be developed. We previously found that the proteolytic cleavage of Reelin within Reelin repeat 3 (N-t site) abolishes Reelin activity in vitro, but it remains controversial as to whether this effect occurs in vivo Here we partially purified the enzyme that mediates the N-t cleavage of Reelin from the culture supernatant of cerebral cortical neurons...
February 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28212525/ablation-of-ferroptosis-regulator-glutathione-peroxidase-4-in-forebrain-neurons-promotes-cognitive-impairment-and-neurodegeneration
#3
William Sealy Hambright, Rene Solano Fonseca, Liuji Chen, Ren Na, Qitao Ran
Synaptic loss and neuron death are the underlying cause of neurodegenerative diseases such as Alzheimer's disease (AD); however, the modalities of cell death in those diseases remain unclear. Ferroptosis, a newly identified oxidative cell death mechanism triggered by massive lipid peroxidation, is implicated in the degeneration of neurons populations such as spinal motor neurons and midbrain neurons. Here, we investigated whether neurons in forebrain regions (cerebral cortex and hippocampus) that are severely afflicted in AD patients might be vulnerable to ferroptosis...
February 1, 2017: Redox Biology
https://www.readbyqxmd.com/read/28212172/cognitive-decline-associated-with-anesthesia-and-surgery-in-the-elderly-does-this-contribute-to-dementia-prevalence
#4
Lisbeth Evered, David A Scott, Brendan Silbert
PURPOSE OF REVIEW: To provide an update on the current state of research investigating the effects of anesthesia and surgery on cognition in the elderly, including consideration of overlap with cognitive disorders in the community. RECENT FINDINGS: The studies reviewed here identify detrimental effects of anesthesia and surgery on cognition in a proportion of elderly individuals. Animal models demonstrate an association between anesthetic agents and Alzheimer's disease pathology...
February 15, 2017: Current Opinion in Psychiatry
https://www.readbyqxmd.com/read/28212021/discovery-and-development-of-1-2-bromophenyl-sulfonyl-5-methoxy-3-4-methyl-1-piperazinyl-methyl-1h-indole-dimesylate-monohydrate-suvn-502-a-novel-potent-selective-and-orally-active-serotonin-6-5-ht6-receptor-antagonist-for-potential-treatment-of-alzheimer-s
#5
Ramakrishna Nirogi, Anil Shinde, Rama Sastry Kambhampati, Abdul Rasheed Mohammed, Sangram Keshari Saraf, Rajesh Kumar Badange, Thrinath Reddy Bandyala, Venugopalarao Bhatta, Kumar Bojja, Veena Reballi, Ramkumar Subramanian, Vijay Benade, Raghava Choudary Palacharla, Gopinadh Bhyrapuneni, Pradeep Jayarajan, Vinod Goyal, Venkat Jasti
Optimization of a novel series of 3-(piperazinylmethyl) indole derivatives as 5-hydroxytryptamine-6 receptor (5-HT6R) antagonists resulted in identification of 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate monohydrate (5al, SUVN-502) as a clinical candidate for potential treatment of cognitive disorders. It has high affinity at human 5-HT6R (Ki = 2.04 nM) and selectivity over 100 target sites which include receptors, enzymes, peptides, growth factors, ion channels, steroids, immunological factors, second messengers, and prostaglandins...
February 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28211900/amyloid-%C3%AE-oligomers-interact-with-neurexin-and-diminish-neurexin-mediated-excitatory-presynaptic-organization
#6
Yusuke Naito, Yuko Tanabe, Alfred Kihoon Lee, Edith Hamel, Hideto Takahashi
Alzheimer's disease (AD) is characterized by excessive production and deposition of amyloid-beta (Aβ) proteins as well as synapse dysfunction and loss. While soluble Aβ oligomers (AβOs) have deleterious effects on synapse function and reduce synapse number, the underlying molecular mechanisms are not well understood. Here we screened synaptic organizer proteins for cell-surface interaction with AβOs and identified a novel interaction between neurexins (NRXs) and AβOs. AβOs bind to NRXs via the N-terminal histidine-rich domain (HRD) of β-NRX1/2/3 and alternatively-spliced inserts at splicing site 4 of NRX1/2...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211811/acidity-and-acid-sensing-ion-channels-in-the-normal-and-alzheimer-s-disease-brain
#7
Eric B Gonzales, Nathalie Sumien
Alzheimer's disease prevalence has reached epidemic proportion with very few treatment options, which are associated with a multitude of side effects. A potential avenue of research for new therapies are protons, and their associated receptor: acid-sensing ion channels (ASIC). Protons are often overlooked neurotransmitters, and proton-gated currents have been identified in the brain. Furthermore, ASICs have been determined to be crucial for proper brain function. While there is more work to be done, this review is intended to highlight protons as neurotransmitters and their role along with the role of ASICs within physiological functioning of the brain...
February 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28211452/early-onset-and-delayed-onset-poststroke-dementia-revisiting-the-mechanisms
#8
REVIEW
Vincent C T Mok, Bonnie Y K Lam, Adrian Wong, Ho Ko, Hugh S Markus, Lawrence K S Wong
Incident stroke has long been recognized to cause dementia shortly after the event. Patients who survive stroke without early-onset poststroke dementia (PSD) are at a high risk of developing dementia months to years after the initial stroke incident, which has generated enthusiasm for exploring treatments to prevent delayed-onset PSD in survivors of stroke. However, results from clinical trials completed in the past 10-15 years have been disappointing. In light of these results, the present Review revisits the mechanisms of both early-onset and delayed-onset PSD and proposes preventive strategies and directions for future clinical trials...
February 17, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28210978/future-directions-in-imaging-neurodegeneration
#9
REVIEW
Joseph C Masdeu
Neuroimaging comprises a powerful set of instruments to diagnose various neurodegenerative disorders, clarifies their neurobiology, and monitors their treatment. Magnetic resonance imaging depicts volume changes, as well as abnormalities in functional and structural connectivity. Positron emission tomography (PET) allows for the quantification of regional cerebral metabolism, characteristically altered in Alzheimer's disease, amyotrophic lateral sclerosis, diffuse Lewy-body disease, and the frontotemporal dementias...
January 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28210868/cognitive-impairment-and-dementia-a-new-emerging-complication-of-type-2-diabetes-the-diabetologist-s-perspective
#10
Rafael Simó, Andreea Ciudin, Olga Simó-Servat, Cristina Hernández
Type 2 diabetes mellitus (T2D) and Alzheimer's disease (AD) are two of the most common diseases of aging around the world. Given the frequency with which T2D and AD occur, the notion that people with T2D may be at increased risk for AD has large societal consequences, and understanding the mechanistic links between these diseases is imperative for the development of effective AD prevention and treatment strategies. Apart from being an accelerator of AD, T2D is associated with a progressive cognitive decline...
February 16, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/28210222/icariside-ii-a-broad-spectrum-anti-cancer-agent-reverses-beta-amyloid-induced-cognitive-impairment-through-reducing-inflammation-and-apoptosis-in-rats
#11
Yuanyuan Deng, Long Long, Keke Wang, Jiayin Zhou, Lingrong Zeng, Lianzi He, Qihai Gong
Beta-amyloid (Aβ) deposition, associated neuronal apoptosis and neuroinflammation are considered as the important factors which lead to cognitive deficits in Alzheimer's disease (AD). Icariside II (ICS II), an active flavonoid compound derived from Epimedium brevicornum Maxim, has been extensively used to treat erectile dysfunction, osteoporosis and dementia in traditional Chinese medicine. Recently, ICS II attracts great interest due to its broad-spectrum anti-cancer property. ICS II shows an anti-inflammatory potential both in cancer treatment and cerebral ischemia-reperfusion...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28208831/resveratrol-and-grape-extract-loaded-solid-lipid-nanoparticles-for-the-treatment-of-alzheimer-s-disease
#12
Joana A Loureiro, Stephanie Andrade, Ana Duarte, Ana Rute Neves, Joana Fontes Queiroz, Cláudia Nunes, Emmanuel Sevin, Laurence Fenart, Fabien Gosselet, Manuel A N Coelho, Maria Carmo Pereira
The aggregation of amyloid-β peptide (Aβ) has been linked to the formation of neuritic plaques, which are pathological hallmarks of Alzheimer's disease (AD). Various natural compounds have been suggested as therapeutics for AD. Among these compounds, resveratrol has aroused great interest due to its neuroprotective characteristics. Here, we provide evidence that grape skin and grape seed extracts increase the inhibition effect on Aβ aggregation. However, after intravenous injection, resveratrol is rapidly metabolized into both glucuronic acid and sulfate conjugations of the phenolic groups in the liver and intestinal epithelial cells (within less than 2 h), which are then eliminated...
February 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28208063/white-matter-lesions-and-the-cholinergic-deficit-in-aging-and-mild-cognitive-impairment
#13
Nils Richter, Anne Michel, Oezguer A Onur, Lutz Kracht, Markus Dietlein, Marc Tittgemeyer, Bernd Neumaier, Gereon R Fink, Juraj Kukolja
In Alzheimer's disease (AD), white matter lesions (WMLs) are associated with an increased risk of progression from mild cognitive impairment (MCI) to dementia, while memory deficits have, at least in part, been linked to a cholinergic deficit. We investigated the relationship between WML load assessed with the Scheltens scale, cerebral acetylcholinesterase (AChE) activity measured with [(11)C]N-methyl-4-piperidyl acetate PET, and neuropsychological performance in 17 patients with MCI due to AD and 18 cognitively normal older participants...
January 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28205585/neuronally-directed-effects-of-rxr-activation-in-a-mouse-model-of-alzheimer-s-disease
#14
M M Mariani, T Malm, R Lamb, T R Jay, L Neilson, B Casali, L Medarametla, G E Landreth
Alzheimer's disease (AD) is characterized by extensive neuron loss that accompanies profound impairments in memory and cognition. We examined the neuronally directed effects of the retinoid X receptor agonist bexarotene in an aggressive model of AD. We report that a two week treatment of 3.5 month old 5XFAD mice with bexarotene resulted in the clearance of intraneuronal amyloid deposits. Importantly, neuronal loss was attenuated by 44% in the subiculum in mice 4 months of age and 18% in layer V of the cortex in mice 8 months of age...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203484/lw-afc-effects-on-n-glycan-profile-in-senescence-accelerated-mouse-prone-8-strain-a-mouse-model-of-alzheimer-s-disease
#15
Jianhui Wang, Xiaorui Cheng, Ju Zeng, Jiangbei Yuan, Zhongfu Wang, Wenxia Zhou, Yongxiang Zhang
Glycosylation is one of the most common eukaryotic post-translational modifications, and aberrant glycosylation has been linked to many diseases. However, glycosylation and glycome analysis is a significantly challenging task. Although several lines of evidence have indicated that protein glycosylation is defective in Alzheimer's disease (AD), only a few studies have focused on AD glycomics. The etiology of AD is unclear and there are no effective disease-modifying treatments for AD. In this study, we found that the object recognition memory, passive avoidance, and spatial learning and memory of senescence-accelerated mouse prone 8 (SAMP8) strain, an AD animal model, were deficient, and LW-AFC, which was prepared from the traditional Chinese medicine prescription Liuwei Dihuang decoction, showed beneficial effects on the deterioration of cognitive capability in SAMP8 mice...
February 2017: Aging and Disease
https://www.readbyqxmd.com/read/28199869/antipsychotic-treatment-effects-on-cardiovascular-cancer-infection-and-intentional-self-harm-as-cause-of-death-in-patients-with-alzheimer-s-dementia
#16
R-E Nielsen, A Lolk, M Rodrigo-Domingo, J-B Valentin, K Andersen
BACKGROUND: Alzheimer's disease (AD), the most common disease causing dementia, is linked to increased mortality. However, the effect of antipsychotic use on specific causes of mortality has not yet been investigated thoroughly. METHODS: Utilizing the Danish nationwide registers, we defined a cohort of patients diagnosed with AD. Utilizing separate Cox regressions for specific causes of mortality, we investigated the effects of cumulative antipsychotic dosage after diagnosis and current antipsychotic exposure in the time period 2000-2011...
December 12, 2016: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/28199036/edaravone-attenuates-intracerebroventricular-streptozotocin-induced-cognitive-impairment-in-rats
#17
K H Reeta, Devendra Singh, Y K Gupta
Alzheimer's disease is a major cause of dementia worldwide. Edaravone, a potent free radical scavenger, is reported to be neuroprotective. The present study was designed to investigate the effect of chronic edaravone administration on intracerebroventricular-streptozotocin (ICV-STZ) induced cognitive impairment in male Wistar rats. Cognitive impairment was developed by single ICV-STZ (3 mg/kg) injection bilaterally on day 1. Edaravone (1, 3 and 10 mg/kg, orally, once daily) was administered for 28 days. Morris water maze and passive avoidance tests were used to assess cognitive functions at baseline and on days 14 and 28...
February 15, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28198563/frequency-and-predictors-of-analgesic-prescribing-in-u-s-nursing-home-residents-with-persistent-pain
#18
Kevin M Fain, G Caleb Alexander, David D Dore, Jodi B Segal, Andrew R Zullo, Carlos Castillo-Salgado
OBJECTIVES: To quantify prescription analgesic use of elderly nursing home (NH) residents with persistent noncancer pain and to identify individual and facility traits associated with no treatment. DESIGN: Cross-sectional study. SETTING: Linked Minimum Data Set (MDS) assessments; Online Survey, Certification and Reporting (OSCAR) records; and Medicare Part D claims. PARTICIPANTS: Individuals aged 65 and older with persistent noncancer pain were identified from a cross-section of all long-stay U...
February 2017: Journal of the American Geriatrics Society
https://www.readbyqxmd.com/read/28197195/myricetin-protects-hippocampal-ca3-pyramidal-neurons-and-improves-learning-and-memory-impairments-in-rats-with-alzheimer-s-disease
#19
Matin Ramezani, Niloufar Darbandi, Fariba Khodagholi, Azam Hashemi
There is currently no treatment for effectively slowing the progression of Alzheimer's disease, so early prevention is very important. Numerous studies have shown that flavonoids can improve memory impairment. The present study investigated the effects of myricetin, a member of the flavonoids, on intracerebroventricular streptozotocin induced neuronal loss and memory impairment in rat models of Alzheimer's disease. Myricetin at 5 or 10 mg/kg was intraperitoneally injected into rats over 21 days. Control rats were treated with 10 mL/kg saline...
December 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28197174/extremely-low-frequency-electromagnetic-fields-stimulation-modulates-autoimmunity-and-immune-responses-a-possible-immuno-modulatory-therapeutic-effect-in-neurodegenerative-diseases
#20
REVIEW
Fabio Guerriero, Giovanni Ricevuti
Increasing evidence shows that extremely low frequency electromagnetic fields (ELF-EMFs) stimulation is able to exert a certain action on autoimmunity and immune cells. In the past, the efficacy of pulsed ELF-EMFs in alleviating the symptoms and the progression of multiple sclerosis has been supported through their action on neurotransmission and on the autoimmune mechanisms responsible for demyelination. Regarding the immune system, ELF-EMF exposure contributes to a general activation of macrophages, resulting in changes of autoimmunity and several immunological reactions, such as increased reactive oxygen species-formation, enhanced phagocytic activity and increased production of chemokines...
December 2016: Neural Regeneration Research
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