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https://www.readbyqxmd.com/read/28537855/multifocal-primary-cutaneous-nodular-amyloidosis
#1
Martha Emily Matsumoto, Mary-Katharine Collins, Anastasios Raptis, Jaroslaw Jedrych, Timothy Patton
Nodular cutaneous amyloidosis (NCA), the least common form of primary cutaneous amyloidosis, is characterized clinically by waxy, purpuric plaques and nodules and histologically by amyloid deposits in the dermis and subcutaneous tissue. We present a patient who developed multiple, non-contiguous NCA lesions over a three year period without evidence of systemic disease. We reviewed the literature and found few other cases of this unusual presentation.
May 15, 2017: Dermatology Online Journal
https://www.readbyqxmd.com/read/28535056/solid-state-nmr-structure-based-inhibitor-design-to-achieve-selective-inhibition-of-the-parallel-in-register-%C3%AE-sheet-versus-antiparallel-iowa-mutant-%C3%AE-amyloid-fibrils
#2
Qinghui Cheng, Wei Qiang
Solid-state nuclear magnetic resonance (ssNMR) spectroscopy has been widely applied to characterize the high-resolution structures of β-amyloid (Aβ) fibrils. While these structures provide crucial molecular insights on the deposition of amyloid plaques in Alzheimer's diseases (AD), ssNMR structures have been rarely used so far as basis for designing inhibitors. It remains a challenge because the ssNMR-based Aβ fibrils structures were usually obtained with sparsely-isotope-labeled peptides with limited experimental constraints, where the structural models, especially the side-chain coordinates showed restricted precision...
May 23, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28534084/the-emerging-link-between-o-glcnacylation-and-neurological-disorders
#3
REVIEW
Xiaofeng Ma, He Li, Yating He, Junwei Hao
O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is involved in the regulation of many cellular cascades and neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. In the brain, the expression of O-GlcNAcylation is notably heightened, as is that of O-linked N-acetylglucosaminyltransferase (OGT) and β-N-acetylglucosaminidase (OGA), the presence of which is prominent in many regions of neurological importance. Most importantly, O-GlcNAcylation is believed to contribute to the normal functioning of neurons; conversely, its dysregulation participates in the pathogenesis of neurological disorders...
May 22, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28533411/bidirectional-regulation-of-a%C3%AE-levels-by-presenilin-1
#4
Victor Bustos, Maria V Pulina, Yildiz Kelahmetoglu, Subhash C Sinha, Fred S Gorelick, Marc Flajolet, Paul Greengard
Alzheimer's disease (AD) is characterized by accumulation of the β-amyloid peptide (Aβ), which is generated through sequential proteolysis of the amyloid precursor protein (APP), first by the action of β-secretase, generating the β-C-terminal fragment (βCTF), and then by the Presenilin 1 (PS1) enzyme in the γ-secretase complex, generating Aβ. γ-Secretase is an intramembranous protein complex composed of Aph1, Pen2, Nicastrin, and Presenilin 1. Although it has a central role in the pathogenesis of AD, knowledge of the mechanisms that regulate PS1 function is limited...
May 22, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28531131/the-role-of-interleukin-18-oxidative-stress-and-metabolic-syndrome-in-alzheimer-s-disease
#5
REVIEW
Johanna O Ojala, Elina M Sutinen
The role of interleukins (ILs) and oxidative stress (OS) in precipitating neurodegenerative diseases including sporadic Alzheimer's disease (AD), requires further clarification. In addition to neuropathological hallmarks-extracellular neuritic amyloid-β (Aβ) plaques, neurofibrillary tangles (NFT) containing hyperphosphorylated tau and neuronal loss-chronic inflammation, as well as oxidative and excitotoxic damage, are present in the AD brain. The pathological sequelae and the interaction of these events during the course of AD need further investigation...
May 21, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28530185/effect-of-gnp-functionalisation-and-multiple-n-methylation-of-%C3%AE-amyloid-residue-32-37-on-gram-positive-bacterium
#6
Nanjundaswamy Marishetty Hemmaragala, Heidi Abrahamse, Blassan P George
In the previous report, the authors showed the gold nanoparticle (GNP) functionalised multiple N-methylated fragments of the residue (32-37) of beta (β)-amyloid protein (1-42), CGGIGLMVG and CGGGGGIGLMVG toward disruption of β-amyloid (1-42), the predominant component of senile plaques. Herein the in vitro antimicrobial activities of both normal and multiple N-methylated sequences of CGGIGLMVG and CGGGGGIGLMVG were screened and it was found that all the eight sequences including four (non-functionalised with GNP) to possess activity against both Gram-positive [Staphylococcus aureus (ATCC 43300) and Enterococcus faecalis (ATCC 5129)] and Gram-negative [Escherichia coli (ATCC 35218), Pseudomonas aeruginosa (ATCC 27853) and Klebsiella pneumoniae (ATCC 700603)] bacteria...
June 2017: IET Nanobiotechnology
https://www.readbyqxmd.com/read/28528968/amylin-and-its-g-protein-coupled-receptor-a-probable-pathological-process-and-drug-target-for-alzheimer-s-disease
#7
REVIEW
Wei Qiao Qiu
G-protein-coupled receptors (GPCRs) are shown to be involved in Alzheimer's disease (AD) pathogenesis. However, because GPCRs include a large family of membrane receptors, it is unclear which specific GPCR or pathway with rational ligands can become effective therapeutic targets for AD. Amylin receptor (AmR) is a GPCR that mediates several activities, such as improving glucose metabolism, relaxing cerebrovascular structure, modulating inflammatory reactions and potentially enhancing neural regeneration. Recent studies show that peripheral treatments with amylin or its clinical analog, pramlintide, reduced several components of AD pathology, including amyloid plaques, tauopathy, neuroinflammation and other components in the brain, corresponding with improved learning and memory in AD mouse models...
May 18, 2017: Neuroscience
https://www.readbyqxmd.com/read/28527218/the-mechanisms-of-action-of-curcumin-in%C3%A2-alzheimer-s-disease
#8
Mengxi Tang, Changiz Taghibiglou
Alzheimer's disease (AD) is a neurodegenerative disorder of the elderly. As the prevalence of AD rises in the 21st century, there is an urgent need for the development of effective pharmacotherapies. Currently, drug treatments target the symptoms of the disease and do not modify or halt the disease progress. Thus, natural compounds have been investigated for their ability to treat AD. This review examines the efficacy of curcumin, a polyphenol derived from turmeric herb, to treat AD. We summarize the in vivo and in vitro research describing the mechanisms of action in which curcumin modifies AD pathology: curcumin inhibits the formation and promotes the disaggregation of amyloid-β plaques, attenuates the hyperphosphorylation of tau and enhances its clearance, binds copper, lowers cholesterol, modifies microglial activity, inhibits acetylcholinesterase, mediates the insulin signaling pathway, and is an antioxidant...
May 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28520803/multiple-modality-biomarker-prediction-of-cognitive-impairment-in-prospectively-followed-de-novo-parkinson-disease
#9
Chelsea Caspell-Garcia, Tanya Simuni, Duygu Tosun-Turgut, I-Wei Wu, Yu Zhang, Mike Nalls, Andrew Singleton, Leslie A Shaw, Ju-Hee Kang, John Q Trojanowski, Andrew Siderowf, Christopher Coffey, Shirley Lasch, Dag Aarsland, David Burn, Lana M Chahine, Alberto J Espay, Eric D Foster, Keith A Hawkins, Irene Litvan, Irene Richard, Daniel Weintraub
OBJECTIVES: To assess the neurobiological substrate of initial cognitive decline in Parkinson's disease (PD) to inform patient management, clinical trial design, and development of treatments. METHODS: We longitudinally assessed, up to 3 years, 423 newly diagnosed patients with idiopathic PD, untreated at baseline, from 33 international movement disorder centers. Study outcomes were four determinations of cognitive impairment or decline, and biomarker predictors were baseline dopamine transporter (DAT) single photon emission computed tomography (SPECT) scan, structural magnetic resonance imaging (MRI; volume and thickness), diffusion tensor imaging (mean diffusivity and fractional anisotropy), cerebrospinal fluid (CSF; amyloid beta [Aβ], tau and alpha synuclein), and 11 single nucleotide polymorphisms (SNPs) previously associated with PD cognition...
2017: PloS One
https://www.readbyqxmd.com/read/28514851/blood-brain-barrier-penetrating-biologic-tnf-%C3%AE-inhibitor-for-alzheimer-s-disease
#10
Rudy Chang, Jillian Knox, Jae Chang, Aram Derbedrossian, Vitaly Vasilevko, David Cribbs, Ruben J Boado, William M Pardridge, Rachita Sumbria
OBJECTIVE: Tumor necrosis factor alpha (TNF-α) driven processes are involved at multiple stages of Alzheimer's disease (AD) pathophysiology and disease progression. Biologic TNF-α inhibitors (TNFIs) are the most potent class of TNFIs but cannot be developed for AD since these macromolecules do not cross the blood-brain barrier (BBB). A BBB-penetrating TNFI was engineered by the fusion of the extracellular domain of the type II human TNF receptor (TNFR) to a chimeric monoclonal antibody (MAb) against the mouse transferrin receptor (TfR), designated as the cTfRMAb-TNFR fusion protein...
May 17, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28514831/hypericum-perforatum-extract-attenuates-behavioral-biochemical-and-neurochemical-abnormalities-in-aluminum-chloride-induced-alzheimer-s-disease-rats
#11
Zheng Cao, Fan Wang, Chunyu Xiu, Jian Zhang, Yanfei Li
Alzheimer's disease (AD) is a progressive and ultimately fatal neurodegenerative diseases. Aluminum, a neurotoxic metal, is considered as the pathological hallmark and contributing factor of AD. Hypericum perforatum extract (HPE) is a neuroprotective agent that can prevent neurodegenerative pathologies through antioxidants, anti-inflammatory and regulating neurotransmitter release in animal model of neuropathy. The present study aimed to identify the potential neuroprotective of HPE on AlCl3-induced AD rats...
May 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28512130/combination-therapy-with-octyl-gallate-and-ferulic-acid-improves-cognition-and-neurodegeneration-in-a-transgenic-mouse-model-of-alzheimer-disease
#12
Takashi Mori, Naoki Koyama, Jun Tan, Tatsuya Segawa, Masahiro Maeda, Terrence Town
To date, there is no effective Alzheimer disease (AD) modifying therapy. Nonetheless, combination therapy holds promise, and nutraceuticals (natural dietary compounds with therapeutic properties) and their synthetic derivatives are well-tolerated candidates. We tested whether combination therapy with octyl gallate (OG) and ferulic acid (FA) improves cognition and mitigates AD-like pathology in the PSAPP transgenic mouse model of cerebral amyloidosis. One-year-old mice with established β-amyloid plaques received daily doses of OG and FA alone or in combination for 3 months...
May 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28509609/amyloid-and-fdg-pet-in-sporadic-creutzfeldt-jakob-disease-correlation-with-pathological-prion-protein-in-neuropathology
#13
Jordi A Matías-Guiu, Carmen Guerrero-Márquez, María Nieves Cabrera-Martín, Ulises Gómez-Pinedo, María Romeral, Diego Mayo, Jesús Porta-Etessam, Teresa Moreno-Ramos, José Luis Carreras, Jorge Matías-Guiu
INTRODUCTION: The role of positron emission tomography (PET) in Creutzfeldt-Jakob disease is less defined than in other neurodegenerative diseases. We studied the correlation between the uptake of (18)F-florbetaben and (18)F-fluorodeoxyglucose with pathological prion protein deposition in histopathology in a case. METHODS: A patient with 80 y old with a rapid neurological deterioration with a confirmed diagnosis of CJD was studied. PET and MRI studies were performed between 13-20 d before the death...
May 16, 2017: Prion
https://www.readbyqxmd.com/read/28509380/amyloid-is-essential-but-insufficient-for-alzheimer-causation-addition-of-subcellular-cofactors-is-required-for-dementia
#14
REVIEW
Jeffrey Fessel
OBJECTIVE: The aim of this study is to examine the hypotheses stating the importance of amyloid or of its oligomers in the pathogenesis of Alzheimer's disease (AD). METHODS: Published studies were examined. RESULTS: The importance of amyloid in the pathogenesis of AD is well established, yet accepting it as the main cause for AD is problematic, because amyloid-centric treatments have provided no clinical benefit and about one-third of cognitively normal, older persons have cerebral amyloid plaques...
May 16, 2017: International Journal of Geriatric Psychiatry
https://www.readbyqxmd.com/read/28505976/in-vivo-detection-of-gray-matter-neuropathology-in-the-3xtg-mouse-model-of-alzheimer-s-disease-with-diffusion-tensor-imaging
#15
Wanda M Snow, Ryan Dale, Zoe O'Brien-Moran, Richard Buist, Danial Peirson, Melanie Martin, Benedict C Albensi
A diagnosis of Alzheimer's disease (AD), a neurodegenerative disorder accompanied by severe functional and cognitive decline, is based on clinical findings, with final confirmation of the disease at autopsy by the presence of amyloid-β (Aβ) plaques and neurofibrillary tangles. Given that microstructural brain alterations occur years prior to clinical symptoms, efforts to detect brain changes early could significantly enhance our ability to diagnose AD sooner. Diffusion tensor imaging (DTI), a type of MRI that characterizes the magnitude, orientation, and anisotropy of the diffusion of water in tissues, has been used to infer neuropathological changes in vivo...
May 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28505972/alzheimer-s-disease-associated-cerebrospinal-fluid-csf-biomarkers-do-not-correlate-with-csf-volumes-or-csf-production-rate
#16
Mikael Edsbagge, Ulf Andreasson, Khalid Ambarki, Carsten Wikkelsø, Anders Eklund, Kaj Blennow, Henrik Zetterberg, Mats Tullberg
BACKGROUND: Neuropathologically, Alzheimer's disease (AD) is characterized by accumulation of a 42 amino acid peptide called amyloid-β (Aβ42) in extracellular senile plaques together with intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles and neuronal degeneration. These changes are reflected in the cerebrospinal fluid (CSF), the volumes and production rates of which vary considerably between individuals, by reduced concentration of Aβ42, increased concentration of phosphorylated tau (P-tau) protein, and increased concentration of total tau (T-tau) protein, respectively...
May 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28505967/nfatc2-modulates-microglial-activation-in-the-a%C3%AE-pp-ps1-mouse-model-of-alzheimer-s-disease
#17
Gunjan D Manocha, Atreyi Ghatak, Kendra L Puig, Susan D Kraner, Christopher M Norris, Colin K Combs
Alzheimer's disease (AD) brains are characterized by fibrillar amyloid-β (Aβ) peptide containing plaques and associated reactive microglia. The proinflammatory phenotype of the microglia suggests that they may negatively affect disease course and contribute to behavioral decline. This hypothesis predicts that attenuating microglial activation may provide benefit against disease. Prior work from our laboratory and others has characterized a role for the transcription factor, nuclear factor of activated T cells (NFAT), in regulating microglial phenotype in response to different stimuli, including Aβ peptide...
May 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28505155/oxidative-stress-and-expression-of-insulin-signaling-proteins-in-the-brain-of-diabetic-rats-role-of-nigella-sativa-oil-and-antidiabetic-drugs
#18
Mahmoud Balbaa, Shaymaa A Abdulmalek, Sofia Khalil
BACKGROUND AND OBJECTIVES: Insulin resistance of the brain is a specific form of type2-diabetes mellitus (T2DM) and the active insulin-signaling pathway plays a neuroprotective role against damaging conditions and Alzheimer's progression. The present study identifies the mediated emerging effects of the Nigella sativa oil (NSO) on the memory enhancing process, its anti-oxidative, acetylcholinestrase (AChE) inhibition, anti-brain insulin resistance and anti-amyloidogenic activities. In addition, the possible role of some anti-diabetic drugs in the neuro-protection processes and their effect in combination with NSO and/or the insulin receptor inhibitor IOMe-AG538 were investigated...
2017: PloS One
https://www.readbyqxmd.com/read/28505007/al-amyloidoma-of-the-skin-subcutis-cutaneous-amyloidosis-plasma-cell-dyscrasia-or-a-manifestation-of-primary-cutaneous-marginal-zone-lymphoma
#19
Noreen M Walsh, Ian Marie Lano, Peter Green, Christopher Gallant, Sylvia Pasternak, Thai Yen Ly, Luis Requena, Heinz Kutzner, Andreas Chott, Lorenzo Cerroni
It is unclear whether AL amyloidoma of the skin/subcutis represents a distinct entity, an indolent precursor of systemic amyloidosis, or a manifestation of cutaneous marginal zone lymphoma (cMZL). We collected 10 cases of cutaneous AL amyloidoma in order to better characterize the clinicopathologic features of this elusive entity (M:F=4:6; median age: 62.5 y, range: 31 to 82 y). Nine patients had a solitary nodule or plaque on the lower extremity (n=7), upper extremity (n=1), or chin (n=1). One patient had an AL amyloidoma on the right thigh and a second lesion on the right arm showing histopathologic features of cMZL without amyloid deposits...
May 12, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28502705/bag-1m-co-activates-bace1transcription-through-nf-%C3%AE%C2%BAb-and-accelerates-a%C3%AE-production-and-memory-deficit-in-model-mice-of-alzheimer-s-disease
#20
Zhemin Shi, Yuheng Hong, Kun Zhang, Jingzhao Wang, Lina Zheng, Zhen Zhang, Zhimei Hu, Xiaohui Han, Yawei Han, Ting Chen, Qingbin Yao, Hongmei Cui, Wei Hong
Accumulation of amyloid β protein (Aβ)-containing neuritic plaques in the brain is a neuropathological feature of Alzheimer's disease (AD). The β-site APP-cleaving enzyme 1 (BACE1) is essential for Aβ generation and dysregulation of BACE1 expression may lead to AD pathogenesis. Bcl-2-associated athanogen 1M (BAG-1M), initially identified as an anti-apoptotic protein, has also been found to be highly expressed in the same neurons that contain intracellular amyloid in the hippocampus of AD patient. In this report, we found that over-expression of BAG-1M enhances BACE1-mediated cleavage of amyloid precursor protein (APP) and Aβ production by up-regulating BACE1 gene transcription...
May 11, 2017: Biochimica et Biophysica Acta
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