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https://www.readbyqxmd.com/read/29783682/heat-shock-gene-inactivation-and-protein-aggregation-with-links-to-chronic-diseases
#1
Ian James Martins
The heat shock response involved in protein misfolding is linked to the formation of toxic immunogenic proteins with heat shock proteins (HSP) as regulators of amyloid beta aggregation. The defective amyloid beta trafficking between different intracellular compartments is now relevant to HSPs and autoimmunity. Overnutrition, temperature dysregulation, and stress repress the heat shock gene Sirtuin 1 with the induction of HSP regulated amyloid beta aggregation involved in the autoimmune response. Defective circadian rhythm alterations are connected to inactivation of the peripheral sink amyloid beta clearance pathway and related to insulin resistance, protein aggregation, and autoimmune disease in non-alcoholic fatty liver disease (NAFLD) and various neurodegenerative diseases such as Alzheimer's disease...
May 18, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29782911/estrogen-deficiency-exacerbates-a%C3%AE-induced-memory-impairment-through-enhancement-of-neuroinflammation-amylodogenesis-and-nf-%C3%A4-b-activation-in-ovariectomized-mice
#2
Jaesuk Yun, In Jun Yeo, Chul Ju Hwang, Dong-Young Choi, Hyung-Sik Im, Ji Youg Kim, Won Rak Choi, Myung Hee Jung, Sang-Bae Han, Jin Tae Hong
Estrogen is well known to have a preventative effect in Alzheimer's disease (AD) pathology. Several studies have demonstrated that nuclear factor kappa-B (NF-ĸB) can contribute to the effects of estrogen on the development of AD. We investigated whether NF-ĸB affects amyloid-beta (Aβ)-induced memory impairment in an estrogen-lacking condition. In the present study, nine-week-old Institute cancer research (ICR) mice were ovariectomized to block estrogen stimulation. Ten weeks after the ovariectomization, mice were administered with Aβ (300 pmol) via intracerebroventricular (ICV) infusion for 2 weeks...
May 18, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29782798/regulatory-activities-of-dopamine-and-its-derivatives-towards-metal-free-and-metal-induced-amyloid-%C3%AE-aggregation-oxidative-stress-and-inflammation-in-alzheimer-s-disease
#3
Eunju Nam, Jeffrey S Derrick, Seunghee Lee, Juhye Kang, Jiyeon Han, Shin Jung C Lee, Su Wol Chung, Mi Hee Lim
A catecholamine neurotransmitter, dopamine (DA), is suggested to be linked to the pathology of dementia; however, the involvement of DA and its structural analogues in the pathogenesis of Alzheimer's disease (AD), the most common form of dementia, composed of multiple pathogenic factors has not been clear. Herein, we report that DA and its rationally designed structural derivatives (1-6) based on DA's oxidative transformation are able to modulate multiple pathological elements found in AD [ i.e., metal ions, metal-free amyloid-β (Aβ), metal-bound Aβ (metal-Aβ), and reactive oxygen species (ROS)], with demonstration of detailed molecular-level mechanisms...
May 21, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29782323/role-of-blood-brain-barrier-in-alzheimer-s-disease
#4
Zhiyou Cai, Pei-Feng Qiao, Cheng-Qun Wan, Min Cai, Nan-Kai Zhou, Qin Li
The blood-brain barrier (BBB) is involved in the pathogenesis of Alzheimer's disease (AD). BBB is a highly selective semipermeable structural and chemical barrier which ensures a stable internal environment of the brain and prevents foreign objects invading the brain tissue. BBB dysfunction induces the failure of Aβ transport from brain to the peripheral circulation across the BBB. Especially, decreased levels of LRP-1 (low density lipoprotein receptor-related protein 1) and increased levels of RAGE (receptor for advanced glycation endproducts) at the BBB can cause the failure of Aβ transport...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29782319/the-relationship-between-obstructive-sleep-apnea-and-alzheimer-s-disease
#5
Andreia Andrade, Omonigho M Bubu, Andrew W Varga, Ricardo S Osorio
 Obstructive sleep apnea (OSA) and Alzheimer's disease (AD) are highly prevalent conditions with growing impact on our aging society. While the causes of OSA are now better characterized, the mechanisms underlying AD are still largely unknown, challenging the development of effective treatments. Cognitive impairment, especially affecting attention and executive functions, is a recognized clinical consequence of OSA. A deeper contribution of OSA to AD pathogenesis is now gaining support from several lines of research...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29782310/putative-gonadotropin-releasing-hormone-agonist-therapy-and-dementia-an-application-of-medicare-hospitalization-claims-data
#6
Mark A Smith, Richard L Bowen, Richard Q Nguyen, George Perry, Craig S Atwood, Alfred A Rimm
BACKGROUND: Estrogen and hormone replacement therapies to reduce Alzheimer's disease (AD) have yielded conflicting results. However, this study proposes that the well-characterized increase in serum gonadotropins following menopause or andropause are accountable for the increased risk of developing AD among the elderly population. OBJECTIVE: To determine the role of gonadotropins in the development of AD and investigate gonadotropin-releasing hormone (GnRH) agonist therapy as a potential preventative and/or disease-modifying approach to AD management...
May 16, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29779477/exposure-of-aggregation-prone-segments-is-the-requirement-for-amyloid-fibril-formation
#7
Shreya Pramanik, Basir Ahmad
Arranging into well-organized fibrillar aggregate, commonly known as amyloid fibril is an inherent property of any polypeptide chain. Amyloid fibrils are associated with a number of severe human pathologies like the Alzheimer's disease, Parkinson's disease, type2 diabetes and many more. Recent studies suggest that most of the fibrils are inert and extremely stable, thus could be used for the bio-nanotechnological applications. As the native state is protected by evolution from aggregation under physiological condition, understanding the structure of aggregation precursor state (APS) will be of extreme importance to decode mechanism of its formation and prevention...
May 20, 2018: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/29779175/anthocyanins-improve-hippocampus-dependent-memory-function-and-prevent-neurodegeneration-via-jnk-akt-gsk3%C3%AE-signaling-in-lps-treated-adult-mice
#8
Muhammad Sohail Khan, Tahir Ali, Min Woo Kim, Myeung Hoon Jo, Jong Il Chung, Myeong Ok Kim
Microglia plays a critical role in the brain and protects neuronal cells from toxins. However, over-activation of microglia leads to deleterious effects. Lipopolysaccharide (LPS) has been reported to affect neuronal cells via activation of microglia as well as directly to initiate neuroinflammation. In the present study, we evaluated the anti-inflammatory and anti-oxidative effect of anthocyanins against LPS-induced neurotoxicity in an animal model and in cell cultures. Intraperitoneal injections of LPS (250 μg/kg/day for 1 week) induce ROS production and promote neuroinflammation and neurodegeneration which ultimately leads to memory impairment...
May 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29779041/the-potential-importance-of-myeloid-derived-suppressor-cells-mdscs-in-the-pathogenesis-of-alzheimer-s-disease
#9
REVIEW
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
The exact cause of Alzheimer's disease (AD) is still unknown, but the deposition of amyloid-β (Aβ) plaques and chronic inflammation indicates that immune disturbances are involved in AD pathogenesis. Recent genetic studies have revealed that many candidate genes are expressed in both microglia and myeloid cells which infiltrate into the AD brains. Invading myeloid cells controls the functions of resident microglia in pathological conditions, such as AD pathology. AD is a neurologic disease with inflammatory component where the immune system is not able to eliminate the perpetrator, while, concurrently, it should prevent neuronal injuries induced by inflammation...
May 19, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29775277/cid-9998128-compound-is-a-potential-multi-target-drug-for-alzheimer-s-disease
#10
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/29774745/interplay-between-copper-neprilysin-and-n-truncation-of-%C3%AE-amyloid
#11
Mariusz Mital, Wojciech Bal, Tomasz Frączyk, Simon C Drew
Sporadic Alzheimer's disease (AD) is associated with an inefficient clearance of the β-amyloid (Aβ) peptide from the central nervous system. The protein levels and activity of the Zn2+ -dependent endopeptidase neprilysin (NEP) inversely correlate with brain Aβ levels during aging and in AD. The present study considered the ability of Cu2+ ions to inhibit human recombinant NEP and the role for NEP in generating N-truncated Aβ fragments with high-affinity Cu2+ binding motifs that can prevent this inhibition...
May 18, 2018: Inorganic Chemistry
https://www.readbyqxmd.com/read/29774516/periodic-variation-of-aak1-in-an-a%C3%AE-1-42-induced-mouse-model-of-alzheimer-s-disease
#12
Xue Fu, Meiling Ke, Weihua Yu, Xia Wang, Qian Xiao, Min Gu, Yang Lü
Inhibition of endocytosis in an Alzheimer's disease (AD) model has been shown to be able to prevent amyloid β (Aβ)-induced damage and to exert a beneficial effect in treating AD. Adaptor-associated kinase 1 (AAK1), which binds to the adaptor protein complex 2 (AP-2), regulates the process of clathrin-mediated endocytosis. However, how AAK1 expression varies over the course of AD is unknown. In this study, we investigated AAK1 levels in AD model mice over time. Aβ1-42 was used to establish a mouse AD model, and the Morris water maze test was used to characterize the time course of Aβ1-42 -induced cognition changes...
May 17, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29773015/caffeine-a-potential-protective-agent-against-cognitive-decline-in-alzheimer-s-disease
#13
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
#14
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
#15
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/29772028/randomized-phase-i-trial-hiv-core-003-depletion-of-serum-amyloid-p-component-and-immunogenicity-of-dna-vaccination-against-hiv-1
#16
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
#17
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/29771571/effect-of-weak-combined-static-and-extremely-low-frequency-alternating-magnetic-fields-on-spatial-memory-and-brain-amyloid-%C3%AE-in-two-animal-models-of-alzheimer-s-disease
#18
Natalia V Bobkova, Vadim V Novikov, Natalia I Medvinskaya, Irina Y Aleksandrova, Inna V Nesterova, Eugenii E Fesenko
Subchronic effect of a weak combined magnetic field (MF), produced by superimposing a constant component, 42 µT and an alternating MF of 0.08 µT, which was the sum of two frequencies of 4.38 and 4.88 Hz, was studied in olfactory bulbectomized (OBE) and transgenic Tg (APPswe, PSEN1) mice, which were used as animal models of sporadic and heritable Alzheimer's disease (AD) accordingly. Spatial memory was tested in a Morris water maze on the following day after completion of training trials with the hidden platform removed...
May 17, 2018: Electromagnetic Biology and Medicine
https://www.readbyqxmd.com/read/29765306/microglial-activation-is-modulated-by-captopril-in-vitro-and-in-vivo-studies
#19
Keren Asraf, Nofar Torika, Ron N Apte, Sigal Fleisher-Berkovich
The renin-angiotensin system (RAS) is an important peripheral system involved in homeostasis modulation, with angiotensin II (Ang II) serving as the main effector hormone. The main enzyme involved in Ang II formation is angiotensin-converting enzyme (ACE). ACE inhibitors (ACEIs) such as captopril (Cap) are predominantly used for the management of hypertension. All of the components of the RAS have also been identified in brain. Centrally located hormones such as Ang II can induce glial inflammation. Moreover, in Alzheimer's disease (AD) models, where glial inflammation occurs and is thought to contribute to the propagation of the disease, increased levels of Ang II and ACE have been detected...
2018: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29764704/current-understanding-of-neuroinflammation-after-traumatic-brain-injury-and-cell-based-therapeutic-opportunities
#20
REVIEW
Ye Xiong, Asim Mahmood, Michael Chopp
Traumatic brain injury (TBI) remains a major cause of death and disability worldwide. Increasing evidence indicates that TBI is an important risk factor for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and chronic traumatic encephalopathy. Despite improved supportive and rehabilitative care of TBI patients, unfortunately, all late phase clinical trials in TBI have yet to yield a safe and effective neuroprotective treatment. The disappointing clinical trials may be attributed to variability in treatment approaches and heterogeneity of the population of TBI patients as well as a race against time to prevent or reduce inexorable cell death...
April 24, 2018: Chinese Journal of Traumatology, Zhonghua Chuang Shang za Zhi
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