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Alzheimers disease treatment

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https://www.readbyqxmd.com/read/29775948/novel-3-phenylcoumarin-lipoic-acid-conjugates-as-multi-functional-agents-for-potential-treatment-of-alzheimer-s-disease
#1
Leili Jalili-Baleh, Hamid Nadri, Hamid Forootanfar, Alireza Samzadeh-Kermani, Tuba Tüylü Küçükkılınç, Beyza Ayazgok, Mahban Rahimifard, Maryam Baeeri, Mohsen Doostmohammadi, Loghman Firoozpour, Syed Nasir Abbas Bukhari, Mohammad Abdollahi, Mohammad Reza Ganjali, Saeed Emami, Mehdi Khoobi, Alireza Foroumadi
New series of triazole-containing 3-phenylcoumarin-lipoic acid conjugates were designed as multi-functional agents for treatment of Alzheimer's disease. The target compounds 4a-o were synthesized via the azide-alkyne cycloaddition reaction and their biological activities were primarily evaluated in terms of neuroprotection against H2 O2 -induced cell death in PC12 cells and AChE/BuChE inhibition. The promising compounds 4j and 4i containing four carbons spacer were selected for further biological evaluations...
May 2, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29775538/discovery-of-potent-and-centrally-active-6-substituted-5-fluoro-1-3-dihydro-oxazine-%C3%AE-secretase-bace1-inhibitors-via-active-conformation-stabilization
#2
Kenji Nakahara, Kouki Fuchino, Kazuo Komano, Naoya Asada, Genta Tadano, Tsuyoshi Hasegawa, Takahiko Yamamoto, Yusuke Sako, Masayoshi Ogawa, Chie Unemura, Motoko Hosono, Hisanori Ito, Gaku Sakaguchi, Shigeru Ando, Shuichi Ohnishi, Yasuto Kido, Tamio Fukushima, Deborah Dhuyvetter, Herman Borghys, Harrie J M Gijsen, Yoshinori Yamano, Yasuyoshi Iso, Ken-Ichi Kusakabe
β-Secretase (BACE1) has an essential role in the production of amyloid β peptides that accumulate in patients with Alzheimer's disease (AD). Thus, inhibition of BACE1 is considered to be a disease-modifying approach for the treatment of AD. Our hit-to-lead efforts led to a cellular potent 1,3-dihydro-oxazine 6, which however inhibited hERG and showed high P-gp efflux. The close analog of 5-fluoro-oxazine 8 reduced P-gp efflux; further introduction of electron withdrawing groups at the 6-position improved potency and also mitigated P-gp efflux and hERG inhibition...
May 18, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29775413/human-cerebral-collateral-arteriole-function-in-normal-cognition-mild-cognitive-impairment-and-dementia-subjects
#3
Raymond Q Migrino, Seth Truran, Nina Karamanova, Geidy Serrano, Calvin Madrigal, Hannah A Davies, Jillian Madine, Peter Reaven, Thomas G Beach
Clinical and preclinical studies suggest a link between cardiovascular disease and dementia disorders but the role of collateral brain circulation in cognitive dysfunction remains unknown. We aim to test the hypothesis that leptomeningeal arteriole (LMA) function and response to metabolic stressors differ among dementia, mild cognitive impairment (MCI) and normal cognition (CN) subjects. Following rapid autopsy, LMA were isolated from CN (N=10), MCI (N=12) or dementia subjects (N=42, Alzheimer's disease [AD], vascular dementia [VaD], or Other Dementia) and endothelial and smooth muscle-dependent function were measured at baseline and following exposure to β-amyloid (Aβ42 2 μM), palmitic acid (PA 150 μM) or medin (5μM) and compared...
May 18, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29775277/cid-9998128-compound-is-a-potential-multi-target-drug-for-alzheimer-s-disease
#4
Nguyen Quoc Thai, Zuzana Bednarikova, Miroslav Gancar, Huynh Quang Linh, Chin-Kun Hu, Mai Suan Li, Zuzana Gazova
We have probed capability of small CID 9998128 compound as a potential multi-target drug for the Alzheimer's disease (AD) using in silico and in vitro experiments. By all-atom simulation and MM-PBSA method we have demonstrated that this compound strongly binds to both amyloid beta 42 (Aβ42 ) fibrils and β-secretase and the van der Waals interaction is dominating over the electrostatic interaction in binding affinity. A detailed analysis at the atomic level revealed that indazole in CID 99998128 structure made a major contribution to instability of all studied complexes...
May 18, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29773975/cold-shock-induced-protein-rbm3-but-not-mild-hypothermia-protects-human-sh-sy5y-neuroblastoma-cells-from-mpp-induced-neurotoxicity
#5
Hai-Jie Yang, Xiang Shi, Fei Ju, Bei-Ning Hao, Shuang-Ping Ma, Lei Wang, Bin-Feng Cheng, Mian Wang
The cold shock protein RBM3 can mediate mild hypothermia-related protection in neurodegeneration such as Alzheimer's disease. However, it remains unclear whether RBM3 and mild hypothermia provide same protection in model of Parkinson's disease (PD), the second most common neurodegenerative disorder. In this study, human SH-SY5Y neuroblastoma cells subjected to insult by 1-methyl-4-phenylpyridinium (MPP+ ) served as an in-vitro model of PD. Mild hypothermia (32°C) aggravated MPP+ -induced apoptosis, which was boosted when RBM3 was silenced by siRNA...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29773015/caffeine-a-potential-protective-agent-against-cognitive-decline-in-alzheimer-s-disease
#6
Azhar Hussain, Elsa S Tabrez, Volodymyr Mavrych, Olena Bolgova, Jagannadha Rao Peela
Over the past few decades, caffeine has been well recognized as a stimulant whose effects can be detected particularly in the central nervous system. A stimulating effect of caffeine has been found useful in treating patients with many neurological disorders, including Alzheimer's disease (AD). AD is reported to be a rapidly increasing public health problem with lack of a remedial treatment. However, the assumed protective effects of caffeine against AD are of huge interest. This study substantiates caffeine's role as a potential prevention agent against AD through several epidemiological studies...
2018: Critical Reviews in Eukaryotic Gene Expression
https://www.readbyqxmd.com/read/29772745/tryptophan-containing-dual-neuroprotective-peptides-prolyl-endopeptidase-inhibition-and-caenorhabditis-elegans-protection-from-%C3%AE-amyloid-peptide-toxicity
#7
Paloma Manzanares, Roberto Martínez, Sandra Garrigues, Salvador Genovés, Daniel Ramón, Jose F Marcos, Patricia Martorell
Neuroprotective peptides represent an attractive pharmacological strategy for the prevention or treatment of age-related diseases, for which there are currently few effective therapies. Lactoferrin (LF)-derived peptides (PKHs) and a set of six rationally-designed tryptophan (W)-containing heptapeptides (PACEIs) were characterized as prolyl endopeptidase (PEP) inhibitors, and their effect on β-amyloid peptide (Aβ) toxicity in a Caenorhabditis elegans model of Alzheimer's disease (AD) was evaluated. Two LF-derived sequences, PKH8 and PKH11, sharing a W at the C-terminal end, and the six PACEI heptapeptides (PACEI48L to PACEI53L) exhibited significant in vitro PEP inhibition...
May 16, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29772526/marine-derived-bioactive-compounds-for-treatment-of-alzheimer-s-disease
#8
Sreeja Lakshmi, Parvathi Prakash, Musthafa M Essa, Walid M Qoronfleh, Mohammed Akbar, Byoung-Joon Song, Suresh Kumar, Preetham Elumalai
Alzheimer's disease (AD ) is mounting as social and economic encumbrance which are accompanied by deficits in cognition and memory. Over the past decades, Alzheimer's disease (AD) holds the frontline as one of the biggest healthcare issues in the world. AD is an age related neurodegenerative disorder marked by a decline in memory and an impairment of cognition. Inspite of tedious scientific effort, AD is still devoid of pharmacotherapeutic strategies for treatment as well as prevention. Current treatment strategies using drugs are symbolic in nature as they treat disease manifestation though are found effective in treating cognition...
June 1, 2018: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/29772289/nose-to-brain-drug-delivery-an-update-on-clinical-challenges-and-progress-towards-approval-of-anti-alzheimer-drugs
#9
REVIEW
Mukta Agrawal, Swarnlata Saraf, Shailendra Saraf, Sophia G Antimisiaris, Mahavir Chougule, Sunday A Shoyele, Amit Alexander
According to the Alzheimer Association Report (2017), Alzheimer's disease (AD) is the 6th primary cause of death in the USA, which affects nearly 5.5 million people. In the year 2017 itself, the cost of AD treatment in the USA has been reported to rise to $259 billion. This statistic shows the severity of the disease in the USA which is very much similar across the globe. On the other hand, the treatment remains limited to a few conventional oral medications (approved by FDA). These are mainly acting superficially from mild to the moderate AD...
May 14, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29772028/randomized-phase-i-trial-hiv-core-003-depletion-of-serum-amyloid-p-component-and-immunogenicity-of-dna-vaccination-against-hiv-1
#10
Nicola J Borthwick, Thirusha Lane, Nathifa Moyo, Alison Crook, Jung Min Shim, Ian Baines, Edmund G Wee, Philip N Hawkins, Julian D Gillmore, Tomáš Hanke, Mark B Pepys
BACKGROUND: The failure of DNA vaccination in humans, in contrast to its efficacy in some species, is unexplained. Observational and interventional experimental evidence suggests that DNA immunogenicity may be prevented by binding of human serum amyloid P component (SAP). SAP is the single normal DNA binding protein in human plasma. The drug (R)-1-[6-[(R)-2-carboxypyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC, miridesap), developed for treatment of systemic amyloidosis and Alzheimer's disease, depletes circulating SAP by 95-99%...
2018: PloS One
https://www.readbyqxmd.com/read/29772021/analysis-of-risk-factors-for-mild-cognitive-impairment-based-on-word-list-memory-test-results-and-questionnaire-responses-in-healthy-japanese-individuals-registered-in-an-online-database
#11
Masayo Ogawa, Daichi Sone, Kazushi Maruo, Hiroyuki Shimada, Keisuke Suzuki, Hiroshi Watanabe, Hiroshi Matsuda, Hidehiro Mizusawa
Although the development of effective therapeutic drugs and radical treatment options for dementia and Alzheimer's disease (AD) remains urgent, progress in recent clinical trials of AD drugs has been less than adequate. In order to advance the progress of clinical trials, it is necessary to establish more efficient methods of recruitment. In Japan, there are registration systems stratified by mild cognitive impairment and preclinical and clinical stages of early and advanced stage dementia, but there is no registration system for healthy individuals yet...
2018: PloS One
https://www.readbyqxmd.com/read/29771687/memantine-er-maintains-patient-response-in-moderate-to-severe-alzheimer-s-disease-post-hoc-analyses-from-a-randomized-controlled-clinical-trial-of-patients-treated-with-cholinesterase-inhibitors
#12
George T Grossberg, Gustavo Alva, Suzanne Hendrix, Noel Ellison, Mary C Kane, John Edwards
Memantine extended release (ER) significantly outperformed placebo on co-primary endpoints of Clinician's Interview-based Impression of Change Plus Caregiver Input (CIBIC-Plus) and baseline to endpoint changes on the Severe Impairment Battery (SIB) in a 24-week, randomized trial (NCT00322153) in patients with moderate to severe Alzheimer's disease taking a cholinesterase inhibitor (ChEI). A post hoc analysis compared patients receiving memantine ER/ChEI to placebo/ChEI for time to onset of response and if the response was maintained (achieving improvement at weeks 8, 12, or 18 and maintaining through endpoint/week 24) on the SIB, the Neuropsychiatric Inventory (NPI), CIBIC-Plus, and Activities of Daily Living (ADL) using Fisher exact test...
May 16, 2018: Alzheimer Disease and Associated Disorders
https://www.readbyqxmd.com/read/29770796/suppression-of-mif-induced-neuronal-apoptosis-may-underlie-the-therapeutic-effects-of-effective-components-of-fufang-danshen-in-the-treatment-of-alzheimer-s-disease
#13
Cheng-Jie Liang, Jia-Huang Li, Zhen Zhang, Ju-Yan Zhang, Shu-Qun Liu, Jie Yang
Fufang Danshen (FFDS or Compound Danshen) consists of three Chinese herbs Danshen (Salviae miltiorrhizae radix et rhizome), Sanqi (Notoginseng radix et rhizome) and Tianranbingpian (Borneolum, or D-borneol), which has been show to significantly improve the function of the nervous system and brain metabolism. In this study we explored the possible mechanisms underlying the therapeutic effects of the combination of the effective components of FFDS (Tan IIA, NG-R1 and Borneol) in the treatment of Alzheimer's disease (AD) based on network pharmacology...
May 17, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29770579/cholinesterase-targeting-by-polyphenols-a-therapeutic-approach-for-the-treatment-of-alzheimer-s-disease
#14
REVIEW
Nasimudeen R Jabir, Fayaz Rahman Khan, Shams Tabrez
Alzheimer's disease (AD) is a progressive irreversible neurodegenerative disorder characterized by excessive deposition of β-amyloid (Aβ) oligomers, and neurofibrillary tangles (NFTs), comprising of hyperphosphorylated tau proteins. The cholinergic system has been suggested as the earliest and most affected molecular mechanism that describes AD pathophysiology. Moreover, cholinesterase inhibitors (ChEIs) are the potential class of drugs that can amplify cholinergic activity to improve cognition and global performance and reduce psychiatric and behavioral disturbances...
May 16, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29770277/a-strategy-to-find-novel-candidate-anti-alzheimer-s-disease-drugs-by-constructing-interaction-networks-between-drug-targets-and-natural-compounds-in-medical-plants
#15
Bi-Wen Chen, Wen-Xing Li, Guang-Hui Wang, Gong-Hua Li, Jia-Qian Liu, Jun-Juan Zheng, Qian Wang, Hui-Juan Li, Shao-Xing Dai, Jing-Fei Huang
Background: Alzheimer' disease (AD) is an ultimately fatal degenerative brain disorder that has an increasingly large burden on health and social care systems. There are only five drugs for AD on the market, and no new effective medicines have been discovered for many years. Chinese medicinal plants have been used to treat diseases for thousands of years, and screening herbal remedies is a way to develop new drugs. Methods: We used molecular docking to screen 30,438 compounds from Traditional Chinese Medicine (TCM) against a comprehensive list of AD target proteins...
2018: PeerJ
https://www.readbyqxmd.com/read/29770251/review-of-the-neurological-benefits-of-phytocannabinoids
#16
REVIEW
Joseph Maroon, Jeff Bost
Background: Numerous physical, psychological, and emotional benefits have been attributed to marijuana since its first reported use in 2,600 BC in a Chinese pharmacopoeia. The phytocannabinoids, cannabidiol (CBD), and delta-9-tetrahydrocannabinol (Δ9-THC) are the most studied extracts from cannabis sativa subspecies hemp and marijuana. CBD and Δ9-THC interact uniquely with the endocannabinoid system (ECS). Through direct and indirect actions, intrinsic endocannabinoids and plant-based phytocannabinoids modulate and influence a variety of physiological systems influenced by the ECS...
2018: Surgical Neurology International
https://www.readbyqxmd.com/read/29768996/a-systematic-review-on-donepezil-based-derivatives-as-potential-cholinesterase-inhibitors-for-alzheimer-s-disease
#17
Jan Korabecny, Katarina Spilovska, Eva Mezeiova, Ondrej Benek, Radomir Juza, Daniel Kaping, Ondrej Soukup
Alzheimer's disease (AD) is a multifactorial progressive neurodegenerative disorder characterized by memory loss, disorientation, and gradual deterioration of intellectual capacity. Its etiology has not been elucidated yet. To date, only one therapeutic approach has been approved for the treatment of AD. The pharmacotherapy of AD has relied on non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist - memantine, and acetylcholinesterase (AChE) inhibitors (AChEIs) - tacrine, donepezil, rivastigmine and galantamine...
May 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29768974/brain-phospholipid-precursors-administered-post-injury-reduce-tissue-damage-and-improve-neurological-outcome-in-experimental-traumatic-brain-injury
#18
Orli Thau-Zuchman, Rita Noutel Gomes, Simon Christopher Dyall, Meirion Davis, John V Priestley, Martine Groenendijk, Martijn DE Wilde, Jordi Lopez-Tremoleda, Adina T Michael-Titus
Traumatic brain injury (TBI) leads to cellular loss, destabilisation of membranes, disruption of synapses and altered brain connectivity, and increased risk of neurodegenerative disease. A significant and long-lasting decrease in phospholipids (PL), essential membrane constituents, has recently been reported in plasma and brain tissue, in human and experimental TBI. We hypothesised that supporting PL synthesis post-injury could improve outcome after TBI. We tested this hypothesis using a multi-nutrient combination designed to support the biosynthesis of phospholipids and available for clinical use...
May 17, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29768467/alpha-7-nicotinic-receptors-attenuate-neurite-development-through-calcium-activation-of-calpain-at-the-growth-cone
#19
Justin R King, Nadine Kabbani
The α7 nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel that plays an important role in cellular calcium signaling contributing to synaptic development and plasticity, and is a key drug target for the treatment of neurodegenerative conditions such as Alzheimer's disease. Here we show that α7 nAChR mediated calcium signals in differentiating PC12 cells activate the proteolytic enzyme calpain leading to spectrin breakdown, microtubule retraction, and attenuation in neurite growth. Imaging in growth cones confirms that α7 activation decreases EB3 comet motility in a calcium dependent manner as demonstrated by the ability of α7 nAChR, ryanodine, or IP3 receptor antagonists to block the effect of α7 nAChR on growth...
2018: PloS One
https://www.readbyqxmd.com/read/29768349/comparison-of-multiple-interventions-for-older-adults-with-alzheimer-disease-or-mild-cognitive-impairment-a-prisma-compliant-network-meta-analysis
#20
Jing-Hong Liang, Yong Xu, Lu Lin, Rui-Xia Jia, Hong-Bo Zhang, Lei Hang
BACKGROUND: The increasing prevalence of Alzheimer disease (AD) emphasizes the need for effective treatments. Both pharmacological therapies such as nutrition therapy (NT) and nonpharmacologic therapies including traditional treatment or personalized treatment (e.g., physical exercise, music therapy, computerized cognitive training) have been approved for the treatment of AD or mild cognitive impairment (MCI) in numerous areas. METHODS: The aim of this study was to compare 4 types of interventions, physical exercise (PE), music therapy (MT), computerized cognitive training (CCT), and NT, in older adults with mild to moderate AD or MCI and identify the most effective intervention for their cognitive function...
May 2018: Medicine (Baltimore)
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