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https://www.readbyqxmd.com/read/29345339/the-role-of-cdk5-mediated-drp1-phosphorylation-in-a%C3%AE-1-42-induced-mitochondrial-fission-and-neuronal-apoptosis
#1
Miao-Yu Guo, Lei Shang, Yang-Yang Hu, Li-Ping Jiang, Yu-Ying Wan, Qin-Qin Zhou, Kun Zhang, Hong-Fei Liao, Jing-Lin Yi, Xiao-Jian Han
Alzheimer's disease, one of the most common neurodegenerative diseases, is pathologically characterized by Amyloid beta containing plaques and neurofibrillary tangles. Amyloid beta (Aβ) induces neuronal apoptosis through the intracellular Ca2+ increase, subsequent hyperactivation of cyclin-dependent kinase 5 (Cdk5) and mitochondrial abnormality. Recently, Cdk5 was identified as an upstream regulator of mitochondrial fission during neuronal apoptosis, but the underlying mechanism remains unclear. Here, in vitro phosphorylation assays showed that Cdk5 could phosphorylate the recombinant Drp1 at Serine 579...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29339171/dna-methylation-level-of-the-neprilysin-promoter-in-alzheimer-s-disease-brains
#2
Kenichi Nagata, Tatsuo Mano, Shigeo Murayama, Takaomi C Saido, Atsushi Iwata
Neprilysin (NEP), a membrane-bound metalloprotease, has been shown to play an essential role in the clearance of amyloid beta (Aβ) peptides. Previous studies have reported that NEP expression is downregulated in the normal aging brain as well as in the Alzheimer's disease (AD) brain, providing evidence that the downregulation of NEP expression contributes to the age-dependent deposition of Aβ-containing plaques, a pathological hallmark of AD. However, the mechanisms underlying the downregulation remain unclear...
January 12, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29338754/molecular-and-functional-signatures-in-a-novel-alzheimer-s-disease-mouse-model-assessed-by-quantitative-proteomics
#3
Dong Kyu Kim, Joonho Park, Dohyun Han, Jinhee Yang, Ahbin Kim, Jongmin Woo, Youngsoo Kim, Inhee Mook-Jung
BACKGROUND: Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by the deposition of extracellular amyloid plaques and intracellular neurofibrillary tangles. To understand the pathological mechanisms underlying AD, developing animal models that completely encompass the main features of AD pathologies is indispensable. Although mouse models that display pathological hallmarks of AD (amyloid plaques, neurofibrillary tangles, or both) have been developed and investigated, a systematic approach for understanding the molecular characteristics of AD mouse models is lacking...
January 16, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29337241/differential-effects-of-alzheimer-s-disease-a%C3%AE-40-and-42-on-endocytosis-and-intraneuronal-trafficking
#4
Rajesh S Omtri, Kevin Thompson, Xiojia Tang, Chaitanya C Gali, Ute Panzenboeck, Michael W Davidson, Krishna R Kalari, Karunya K Kadimalla
Anomalous neuronal accumulation of Aβ peptides was shown to affect synaptic transmission and contribute to neurodegeneration in Alzheimer's disease (AD) brain. Neuronal cells internalize amyloid beta (Aβ) peptides from the brain extracellular space even under normal physiological conditions, and these endocytotic pathways go awry during AD progression. We hypothesized that exposure to toxic Aβ species accumulating in AD brain contribute to perturbations in neuronal endocytosis. We have shown substantial down-regulation of KEGG endocytotic pathway genes in AD patient brain regions that accumulate Aβ compared to those in non-demented individuals...
January 11, 2018: Neuroscience
https://www.readbyqxmd.com/read/29337053/oral-ingestion-of-plasmalogens-can-attenuate-the-lps-induced-memory-loss-and-microglial-activation
#5
Md Shamim Hossain, Ayako Tajima, Satoshi Kotoura, Toshihiko Katafuchi
Plasmalogens (Pls) are the special phospholipids which were reported to be reduced in brain and blood samples of Alzheimer's disease (AD) patients, suggested a possibility that an oral ingestion of Pls may prevent the disease progression. Interestingly, the clinical study showed that the daily oral ingestion of Pls among the mild AD patients improved cognition. However, it is unknown of whether the oral ingestion of Pls inhibits the AD like changes in brain e.g., glial activation and accumulation of amyloid beta (Aβ) proteins...
January 11, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29336840/heterozygous-tyrobp-deletion-ploslfin-is-not-a-strong-risk-factor-for-cognitive-impairment
#6
Karri Kaivola, Lilja Jansson, Elmo Saarentaus, Anna Kiviharju, Ville Rantalainen, Johan G Eriksson, Timo E Strandberg, Tuomo Polvikoski, Liisa Myllykangas, Pentti J Tienari
Biallelic loss-of-function mutations in TYROBP and TREM2 cause a rare disease that resembles early-onset frontotemporal dementia with bone lesions called polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). Some PLOSL-causing variants in TREM2 have also been associated with Alzheimer's disease when heterozygous. Here, we studied the PLOSLFINTYROBP deletion that covers 4 of the gene's 5 exons. We genotyped 3220 older Finns (mean age 79, range 58-104) and found 11 deletion carriers (mean age 78, range 60-94)...
December 18, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29334419/a-metallo-pro-drug-to-target-cu-ii-in-the-context-of-alzheimer-s-disease
#7
Amandine Conte-Daban, Vinita Ambike, Régis Guillot, Nicolas Delsuc, Clotilde Policar, Christelle Hureau
Alzheimer's disease and oxidative stress are connected. In the present communication, we report the use of a Mn(II)-based superoxide dismutase mimic ([MnII(L)]+, 1+) as a pro-drug candidate to target Cu(II) associated events, i.e. Cu(II)-induced formation of reactive oxygen species (ROS) and modulation of the amyloid-beta (Abeta) peptide aggregation. Complex 1+ is able to remove Cu(II) from Abeta, stop ROS and prevent alteration of Abeta aggregation as would do the corresponding free ligand LH. Using 1+ instead of LH in further biological applications would have the double advantage to avoid the cell toxicity of LH and to benefit from its proved SOD-like activity...
January 15, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29334222/on-line-preconcentration-in-capillaries-by-multiple-large-volume-sample-stacking-an-alternative-to-immunoassays-for-quantification-of-amyloid-beta-peptides-biomarkers-in-cerebrospinal-fluid
#8
Cedric Crosnier de Lassichere, Thanh Duc Mai, Markus Otto, Myriam Taverna
A novel electrokinetic preconcentration approach, so-called multiple pressure-assisted large-volume sample stacking with an electroosmotic flow pump (M-PA-LVSEP), was developed to allow in-capillary enrichment and separation of analytes from unlimited sample volumes. With this approach, the inherent limitation of in-capillary electrokinetic preconcentrations to the separation capillary volume can be overcome. The M-PA-LVSEP protocol relies on repeated cycles of pressure-assisted electroosmotic pumping and injection of extremely large sample volumes for analyte stacking and sample matrix removal...
January 15, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29332584/multicomponent-reactions-for-multitargeted-compounds-for-alzheimer-s-disease
#9
Lhassane Ismaili, Maria do Carmo Carreiras
Alzheimer's disease (AD) is a multifactorial and fatal neurodegenerative disorder affecting around 35 million people worldwide, which is characterized by decline of cholinergic function, deregulation of amyloid beta (Aβ) oligomers formation and Aβ fibril deposition. Multi-target--directed ligands (MTDLs) have emerged as an original strategy for developing new therapeutic agents on AD. Multicomponent reactions (MCRs) are a useful alternative to sequential multistep syntheses, allowing scaffold diversity and a rapid and easy access to biologically relevant compounds...
January 12, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29332579/alzheimer-s-disease-a-systemic-review-of-substantial-therapeutic-targets-and-the-leading-multi-functional-molecules
#10
Tarana Umar, Nasimul Hoda
Alzheimer's disease (AD) is a fatal neurodegenerative disorder, having a complex aetiology with numerous possible drug targets. There are targets that have been known for years while more new targets and theories have also emerged. Beta amyloid and cholinesterases are the most significant biological targets for finding curative treatment of AD. The major class of drugs used for AD till now has been the Cholinesterase (ChE) inhibitors. Other prevailing models of molecular pathogenesis in AD include neurofibrillary tangles (NFTs) and amyloid deposition, tryptophan degradation pathway, kinase and phosphatase activity imbalance and neuroinflammation...
January 12, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29330135/apbb2-is-associated-with-amphetamine-use-and-plasma-beta-amyloids-in-patients-receiving-methadone-maintenance-treatment
#11
Chia-Chen Liu, Chiu-Ping Fang, Tung-Hsia Liu, Hsiang-Wei Kuo, Shu Chi Liu, Sheng-Chang Wang, Andrew C H Chen, Yu-Li Liu
APBB2, amyloid beta (A4) precursor protein-binding family B member 2, has been reported to be associated with opioid dependence. In this study, we reported the first time that the genetic variants in the APBB2 gene were associated with use of amphetamine in opioid dependent patients undergoing methadone maintenance treatment (MMT). 344 heroin-dependent patients undergoing MMT were recruited and assessed for use of amphetamine and opioids by urine toxicology, withdrawal severity, and side effects. DNAs were genome-widely genotyped for all patients...
January 9, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29329580/evidence-for-the-activation-of-pyroptotic-and-apoptotic-pathways-in-rpe-cells-associated-with-nlrp3-inflammasome-in-the-rodent-eye
#12
Jiangyuan Gao, Jing Z Cui, Eleanor To, Sijia Cao, Joanne A Matsubara
BACKGROUND: Age-related macular degeneration (AMD) is a devastating eye disease causing irreversible vision loss in the elderly. Retinal pigment epithelium (RPE), the primary cell type that is afflicted in AMD, undergoes programmed cell death in the late stages of the disease. However, the exact mechanisms for RPE degeneration in AMD are still unresolved. The prevailing theories consider that each cell death pathway works independently and without regulation of each other. Building upon our previous work in which we induced a short burst of inflammasome activity in vivo, we now investigate the effects of prolonged inflammasome activity on RPE cell death mechanisms in rats...
January 12, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29328990/the-amyloidogenicity-of-the-influenza-virus-pb1-derived-peptide-sheds-light-on-its-antiviral-activity
#13
Yana A Zabrodskaya, Dmitry V Lebedev, Marja A Egorova, Aram A Shaldzhyan, Alexey V Shvetsov, Alexander I Kuklin, Daria S Vinogradova, Nikolay V Klopov, Oleg V Matusevich, Taisiia A Cheremnykh, Rajeev Dattani, Vladimir V Egorov
The influenza virus polymerase complex is a promising target for new antiviral drug development. It is known that, within the influenza virus polymerase complex, the PB1 subunit region from the 1st to the 25th amino acid residues has to be is in an alpha-helical conformation for proper interaction with the PA subunit. We have previously shown that PB1(6-13) peptide at low concentrations is able to interact with the PB1 subunit N-terminal region in a peptide model which shows aggregate formation and antiviral activity in cell cultures...
January 8, 2018: Biophysical Chemistry
https://www.readbyqxmd.com/read/29325805/reduced-plaque-size-and-inflammation-in-the-app23-mouse-model-for-alzheimer-s-disease-after-chronic-application-of-polymeric-nanoparticles-for-cns-targeted-zinc-delivery
#14
Antonietta Vilella, Daniela Belletti, Ann Katrin Sauer, Simone Hagmeyer, Tasnuva Sarowar, Martina Masoni, Natalia Stasiak, John J E Mulvihill, Barbara Ruozi, Flavio Forni, Maria Angela Vandelli, Giovanni Tosi, Michele Zoli, Andreas M Grabrucker
A local dyshomeostasis of zinc ions in the vicinity of amyloid aggregates has been proposed in Alzheimer's disease (AD) due to the sequestration of zinc in senile plaques. While an increase in zinc levels may promote the aggregation of amyloid beta (Aβ), increased brain zinc might also be beneficial rescuing some pathological alterations caused by local zinc deficiency. For example, increased Aβ degradation by metalloproteinases, and a reduction in inflammation can be hypothesized. In addition, zinc may allow a stabilization of the number of synapses in AD brains...
December 27, 2017: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29325447/longitudinal-association-of-amyloid-beta-and-anxious-depressive-symptoms-in-cognitively-normal-older-adults
#15
Nancy J Donovan, Joseph J Locascio, Gad A Marshall, Jennifer Gatchel, Bernard J Hanseeuw, Dorene M Rentz, Keith A Johnson, Reisa A Sperling
OBJECTIVE: To understand the role of depressive symptoms in preclinical Alzheimer's disease, it is essential to define their temporal relationship to Alzheimer's proteinopathies in cognitively normal older adults. The study objective was to examine associations of brain amyloid beta and longitudinal measures of depression and depressive symptom clusters in a cognitively normal sample of older adults. METHOD: A total of 270 community-dwelling, cognitively normal elderly individuals underwent baseline Pittsburgh compound B (PiB) positron emission tomography (PET) measures of cortical aggregate amyloid beta and annual assessments with the 30-item Geriatric Depression Scale (GDS)...
January 12, 2018: American Journal of Psychiatry
https://www.readbyqxmd.com/read/29324921/the-correlation-of-evans-index-with-csf-protein-levels-and-ventriculomegaly
#16
D Papaoikonomou, E Karypidou, P Megagiannis, F Tsolaki-Tagaraki, S Nenopoulou, O Gkatzima, Magda Tsolaki
OBJECTIVE: The role of ventriculomegaly and its interplay between various dementia entities and their pathogenesis, as well as its correlation to the levels of CSF protein markers, remains to be elucidated. Evans index (EI) is a well-established radiological marker in the diagnosis of idiopathic Normal Pressure Hydrocephalus (iNPH), assessing ventricular enlargement. However, there are no previous studies investigating the correlation between EI, age, beta amyloid (Aβ), tau and phosphorylated-tau (p-tau) proteins in the CSF...
September 2017: Hellenic Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/29324783/sirt3-activator-honokiol-attenuates-%C3%AE-amyloid-by-modulating-amyloidogenic-pathway
#17
Sindhu Ramesh, Manoj Govindarajulu, Tyler Lynd, Gwyneth Briggs, Danielle Adamek, Ellery Jones, Jake Heiner, Mohammed Majrashi, Timothy Moore, Rajesh Amin, Vishnu Suppiramaniam, Muralikrishnan Dhanasekaran
Honokiol (poly-phenolic lignan from Magnolia grandiflora) is a Sirtuin-3 (SIRT3) activator which exhibit antioxidant activity and augment mitochondrial functions in several experimental models. Modern evidence suggests the critical role of SIRT3 in the progression of several metabolic and neurodegenerative diseases. Amyloid beta (Aβ), the precursor to extracellular senile plaques, accumulates in the brains of patients with Alzheimer's disease (AD) and is related to the development of cognitive impairment and neuronal cell death...
2018: PloS One
https://www.readbyqxmd.com/read/29323711/hiv-1-increases-extracellular-amyloid-beta-levels-through-neprilysin-regulation-in-primary-cultures-of-human-astrocytes
#18
Marta Martínez-Bonet, M Ángeles Muñoz-Fernández, Susana Álvarez
Since the success of combined antiretroviral therapy, HIV-1-infected individuals are now living much longer. This increased life expectancy is accompanied by a higher prevalence of HIV-1 associated neurocognitive disorders. Rising too is the incidence in these patients of pathological hallmarks of Alzheimer's disease such as increased deposition of amyloid beta protein (Aβ). Although neurons are major sources of Aβ in the brain, astrocytes are the most numerous glial cells, therefore, even a small level of astrocytic Aβ metabolism could make a significant contribution to brain pathology...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29321508/thrombospondin-1-secreted-by-human-umbilical-cord-blood-derived-mesenchymal-stem-cells-rescues-neurons-from-synaptic-dysfunction-in-alzheimer-s-disease-model
#19
Dong Hyun Kim, Hoon Lim, Dahm Lee, Soo Jin Choi, Wonil Oh, Yoon Sun Yang, Jeong Su Oh, Hyun Ho Hwang, Hong Bae Jeon
Alzheimer's disease (AD) is an incurable neurodegenerative disease characterised clinically by learning and memory impairments. Amyloid beta (Aβ) peptide-induced synaptic dysfunction is a pathological process associated with early-stage AD. Here, we show that paracrine action of human umbilical cord blood-derived-mesenchymal stem cells (hUCB-MSCs) protects the hippocampus from synaptic-density loss in in vitro and in vivo AD models. To identify paracrine factors underlying this rescue effect, we analysed hUCB-MSCs' secretome co-cultured with Aβ42-treated mouse hippocampal neurons...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29321137/novel-function-of-ceramide-for-regulation-of-mitochondrial-atp-release-in-astrocytes
#20
Ji-Na Kong, Zhihui Zhu, Yutaka Itokazu, Guanghu Wang, Michael B Dinkins, Liansheng Zhong, Hsuan-Pei Lin, Ahmed Elsherbini, Silvia Leanhart, Xue Jiang, Haiyan Qin, Wenbo Zhi, Stefka D Spassieva, Erhard Bieberich
We reported that amyloid beta peptide (Abeta42) activated neutral sphingomyelinase 2 (nSMase2) thereby increasing the concentration of the sphingolipid ceramide in astrocytes. Here, we show that Abeta42 induced mitochondrial fragmentation in wild type astrocytes, but not in nSMase2-deficient cells or astrocytes treated with Fumonisin B1 (FB1), an inhibitor of ceramide synthases. Unexpectedly, ceramide depletion was concurrent with rapid movements of mitochondria, indicating an unknown function of ceramide for mitochondria...
January 10, 2018: Journal of Lipid Research
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