keyword
MENU ▼
Read by QxMD icon Read
search

alzheimer's disease prion diseases

keyword
https://www.readbyqxmd.com/read/28096242/developing-therapeutics-for-prp-prion-diseases
#1
Kurt Giles, Steven H Olson, Stanley B Prusiner
The prototypical PrP prion diseases are invariably fatal, and the search for agents to treat them spans more than 30 years, with limited success. However, in the last few years, the application of high-throughput screening, medicinal chemistry, and pharmacokinetic optimization has led to important advances. The PrP prion inoculation paradigm provides a robust assay for testing therapeutic efficacy, and a dozen compounds have been reported that lead to meaningful extension in survival of prion-infected mice...
January 17, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28077650/melanin-or-melanin-like-substance-interacts-with-the-n-terminal-portion-of-prion-protein-and-inhibits-abnormal-prion-protein-formation-in-prion-infected-cells
#2
Taichi Hamanaka, Keiko Nishizawa, Yuji Sakasegawa, Ayumi Oguma, Kenta Teruya, Hiroshi Kurahashi, Hideyuki Hara, Suehiro Sakaguchi, Katsumi Doh-Ura
Prion diseases are progressive fatal neurodegenerative illnesses caused by the accumulation of transmissible abnormal prion protein (PrP). To find treatments for prion diseases, we searched for substances from natural resources that inhibit abnormal PrP formation in prion-infected cells. We found that high-molecular-weight components from insect cuticle extracts reduced abnormal PrP levels. The chemical nature of these components was consistent with that of melanin. In fact, synthetic melanin produced from tyrosine or 3-hydroxy-l-tyrosine inhibited abnormal PrP formation...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28059790/combined-creutzfeldt-jakob-jacob-alzheimer-s-disease-cases-are-important-in-search-for-microbes-in-alzheimer-s-disease
#3
Frank O Bastian
The question whether Alzheimer's disease is infectious as brought up in the recent editorial published in the Journal of Alzheimer's Disease is complicated by the controversy whether the causal agent is a microbe or a misfolded host protein (amyloid). The replicating amyloid (prion) theory, based upon data from studies of Creutzfeldt-Jakob disease (CJD) and other transmissible spongiform encephalopathies (TSEs), has been challenged since the prion can be separated from TSE infectivity, and spiroplasma, a wall-less bacterium, has been shown to be involved in the pathogenesis of CJD...
December 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28052060/structural-variation-in-amyloid-%C3%AE-fibrils-from-alzheimer-s-disease-clinical-subtypes
#4
Wei Qiang, Wai-Ming Yau, Jun-Xia Lu, John Collinge, Robert Tycko
Aggregation of amyloid-β peptides into fibrils or other self-assembled states is central to the pathogenesis of Alzheimer's disease. Fibrils formed in vitro by 40- and 42-residue amyloid-β peptides (Aβ40 and Aβ42) are polymorphic, with variations in molecular structure that depend on fibril growth conditions. Recent experiments suggest that variations in amyloid-β fibril structure in vivo may correlate with variations in Alzheimer's disease phenotype, in analogy to distinct prion strains that are associated with different clinical and pathological phenotypes...
January 12, 2017: Nature
https://www.readbyqxmd.com/read/28049644/functional-prions-in-the-brain
#5
REVIEW
Joseph B Rayman, Eric R Kandel
Prions are proteins that can adopt self-perpetuating conformations and are traditionally regarded as etiological agents of infectious neurodegenerative diseases in humans, such as Creutzfeldt-Jakob disease, kuru, and transmissible encephalopathies. More recently, a growing consensus has emerged that prion-like, self-templating mechanisms also underlie a variety of neurodegenerative disorders, including amyotrophic lateral sclerosis, Alzheimer's disease, and Huntington's disease. Perhaps most surprising, not all prion-like aggregates are associated with pathological changes...
January 3, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28040507/visualization-of-prion-like-transfer-in-huntington-s-disease-models
#6
REVIEW
Anne H P Jansen, Kevin L Batenburg, Eline Pecho-Vrieseling, Eric A Reits
Most neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's disease are hallmarked by aggregate formation of disease-related proteins. In various of these diseases transfer of aggregation-prone proteins between neurons and between neurons and glial cells has been shown, thereby initiating aggregation in neighboring cells and so propagating the disease phenotype. Whereas this prion-like transfer is well studied in Alzheimer's and Parkinson's disease, only a few studies have addressed this potential mechanism in Huntington's disease...
December 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27997158/chaperone-like-activity-of-calnuc-prevents-amyloid-aggregation
#7
Madhavi Kanuru, Gopala Krishna Aradhyam
Calnuc is a ubiquitously expressed protein of the EF-hand Ca(2+)-binding superfamily. Previous studies have implicated it in Ca(2+)-sensitive physiological processes, whereas details of its function and involvement in human diseases are lacking. Drawing upon the sequence homology of calnuc with calreticulin, we propose it functions as a molecular chaperone-like protein. In cells under thermal, chemical [urea and guanidinium chloride (GdmCl)], and acidic stress, calnuc exhibits properties similar to those of established chaperone-like proteins (GRP78, spectrin, and α-crystallin), effectively demonstrated by its ability to suppress aggregation of malate dehydrogenase (MDH), alcohol dehydrogenase, and catalase...
December 20, 2016: Biochemistry
https://www.readbyqxmd.com/read/27995109/chitosan-myristate-nanogel-as-an-artificial-chaperone-protects-neuroserpin-from-misfolding
#8
Habib Nazem, Afshin Mohsenifar, Sahar Majdi
BACKGROUND: Molecular chaperon-like activity for protein refolding was studied using nanogel chitosan-myristic acid (CMA) and the protein neuroserpin (NS), a member of the serine proteinase inhibitor superfamily (serpin). MATERIALS AND METHODS: Recombinant his-tag fusion NS was expressed in Escherichia coli. For confirmation of refolding of the purified NS, structural analysis was performed by circular dichroism and spectrofluorometric along with its inhibitory activity, which was assayed by single-chain tissue plasminogen activator...
2016: Advanced Biomedical Research
https://www.readbyqxmd.com/read/27991860/m1-muscarinic-allosteric-modulators-slow-prion-neurodegeneration-and-restore-memory-loss
#9
Sophie J Bradley, Julie-Myrtille Bourgognon, Helen E Sanger, Nicholas Verity, Adrian J Mogg, David J White, Adrian J Butcher, Julie A Moreno, Colin Molloy, Timothy Macedo-Hatch, Jennifer M Edwards, Jurgen Wess, Robert Pawlak, David J Read, Patrick M Sexton, Lisa M Broad, Joern R Steinert, Giovanna R Mallucci, Arthur Christopoulos, Christian C Felder, Andrew B Tobin
The current frontline symptomatic treatment for Alzheimer's disease (AD) is whole-body upregulation of cholinergic transmission via inhibition of acetylcholinesterase. This approach leads to profound dose-related adverse effects. An alternative strategy is to selectively target muscarinic acetylcholine receptors, particularly the M1 muscarinic acetylcholine receptor (M1 mAChR), which was previously shown to have procognitive activity. However, developing M1 mAChR-selective orthosteric ligands has proven challenging...
December 19, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27940601/binding-sites-for-amyloid-%C3%AE-oligomers-and-synaptic-toxicity
#10
Levi M Smith, Stephen M Strittmatter
In Alzheimer's disease (AD), insoluble and fibrillary amyloid-β (Aβ) peptide accumulates in plaques. However, soluble Aβ oligomers are most potent in creating synaptic dysfunction and loss. Therefore, receptors for Aβ oligomers are hypothesized to be the first step in a neuronal cascade leading to dementia. A number of cell-surface proteins have been described as Aβ binding proteins, and one or more are likely to mediate Aβ oligomer toxicity in AD. Cellular prion protein (PrP(C)) is a high-affinity Aβ oligomer binding site, and a range of data delineates a signaling pathway leading from Aβ complexation with PrP(C) to neuronal impairment...
December 9, 2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27940600/the-prion-like-behavior-of-assembled-tau-in-transgenic-mice
#11
Florence Clavaguera, Markus Tolnay, Michel Goedert
Tauopathies constitute neurodegenerative diseases that are characterized by the intracellular deposition of filaments made of hyperphosphorylated tau protein. The pattern of tau deposition in Alzheimer's disease follows a stereotypical progression, with the first lesions appearing in the locus coeruleus and entorhinal cortex, from where they appear to spread to the hippocampus and neocortex. Propagation of pathological tau is also characteristic of argyrophilic grain disease, where the lesions seem to spread through distinct regions of the limbic system...
December 9, 2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27940516/molecular-genetics-of-neurodegenerative-dementias
#12
Flora I Hinz, Daniel H Geschwind
Neurodegenerative dementias are clinically heterogeneous, progressive diseases with frequently overlapping symptoms, such as cognitive impairments and behavior and movement deficits. Although a majority of cases appear to be sporadic, there is a large genetic component that has yet to be fully explained. Here, we review the recent genetic and genomic findings pertaining to Alzheimer's disease, frontotemporal dementia, Lewy body dementia, and prion dementia. In this review, we describe causal and susceptibility genes identified for these dementias and discuss recent research pertaining to the molecular function of these genes...
December 9, 2016: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/27939356/the-origins-of-rimmed-vacuoles-and-granulovacuolar-degeneration-bodies-are-associated-with-the-wnt-signaling-pathway
#13
Yukari Murata-Shinozaki, Tetsuya Takahashi, Tomoyasu Matsubara, Hirofumi Maruyama, Yuishin Izumi, Masayasu Matsumoto
Inclusion-body myositis (IBM) and Alzheimer's disease (AD) are biochemically characterized by the presence of aggregated β-amyloid protein and tau protein. In addition, both diseases are pathologically characterized by vacuolar changes, including rimmed vacuoles (RVs) in IBM and granulovacuolar degeneration (GVD) in AD. Previously, we demonstrated that RVs and GVD bodies are associated with a set of common molecules, leading us to speculate that both RVs and GVD bodies originate from similar structures on the plasma membrane of muscle cells and neuronal cells, namely, the neuromuscular junction (NMJ) and the postsynaptic spine especially in terms of Wnt signaling pathway...
December 7, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27929804/familial-creutzfeldt-jakob-disease-case-report-and-role-of-genetic-counseling-in-post-mortem-testing
#14
Kristin Clift, Kimberly Guthrie, Eric W Klee, Nicole Boczek, Margot Cousin, Patrick Blackburn, Paldeep Atwal
Here we present a case of an asymptomatic 53-year-old woman who sought genetic testing for Familial Creutzfeldt-Jakob Disease (fCJD) after learning that her mother had fCJD. The patient's mother had a sudden onset of memory problems and rapidly deteriorating mental faculties in her late 70s, which led to difficulties ambulating, progressive non-fluent aphasia, dysphagia and death within ∼1 y of symptom onset. The cause of death was reported as "rapid onset dementia." The patient's family, unhappy with the vague diagnosis, researched prion disorders online and aggressively pursued causation and submitted frozen brain tissue from the mother to the National Prion Disease Surveillance Center, where testing revealed a previously described 5-octapeptide repeat insertion (5-OPRI) in the prion protein gene (PRNP) that is known to cause fCJD...
November 2016: Prion
https://www.readbyqxmd.com/read/27928512/extracellular-vesicle-associated-a%C3%AE-mediates-trans-neuronal-bioenergetic-and-ca-2-handling-deficits-in-alzheimer-s-disease-models
#15
Erez Eitan, Emmette R Hutchison, Krisztina Marosi, James Comotto, Maja Mustapic, Saket M Nigam, Caitlin Suire, Chinmoyee Maharana, Gregory A Jicha, Dong Liu, Vasiliki Machairaki, Kenneth W Witwer, Dimitrios Kapogiannis, Mark P Mattson
Alzheimer's Disease (AD) is an age-related neurodegenerative disorder in which aggregation-prone neurotoxic amyloid β-peptide (Aβ) accumulates in the brain. Extracellular vesicles (EVs) are small 50-150 nanometer membrane vesicles that have recently been implicated in the prion-like spread of self-aggregating proteins. Here we report that EVs isolated from AD patient CSF and plasma, from the plasma of two AD mouse models, and from the medium of neural cells expressing familial AD presenilin 1 mutations, destabilize neuronal Ca(2+) homeostasis, impair mitochondrial function, and sensitize neurons to excitotoxicity...
2016: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/27921253/aberrant-alterations-of-mitochondrial-factors-drp1-and-opa1-in-the-brains-of-scrapie-experiment-rodents
#16
Xiao -Dong Yang, Qi Shi, Jing Sun, Yan Lv, Yue Ma, Cao Chen, Kang Xiao, Wei Zhou, Xiao-Ping Dong
The abnormal mitochondrial dynamics has been reported in the brains of some neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), but limitedly described in prion disease. Dynamin-related protein 1 (Drpl) and optic atrophy protein 1 (Opa1) are two essential elements for mitochondria fission and fusion. To evaluate possible changes of mitochondria dynamics during prion infection, the situations of brain Drp1 and Opa1 of scrapie strains 139A, ME7, and S15 mice, as well as 263K-infected hamsters, were analyzed...
December 6, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27916654/prion-like-mechanisms-and-potential-therapeutic-targets-in-neurodegenerative-disorders
#17
REVIEW
Masato Hasegawa, Takashi Nonaka, Masami Masuda-Suzukake
Prion-like propagation of abnormal intracytoplasmic proteins, which are the defining features of major neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), has been proposed. A growing body of evidence strongly suggests that abnormal tau, α-synuclein and TDP-43 have prion-like properties, convert the corresponding normal proteins into abnormal forms, and are transmitted from cell to cell, spreading throughout the brain. This idea is extremely important not only for understanding the pathogenesis and progression of these diseases, but also for the development of molecular therapies...
December 1, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27911827/tau-prions-from-alzheimer-s-disease-and-chronic-traumatic-encephalopathy-patients-propagate-in-cultured-cells
#18
Amanda L Woerman, Atsushi Aoyagi, Smita Patel, Sabeen A Kazmi, Iryna Lobach, Lea T Grinberg, Ann C McKee, William W Seeley, Steven H Olson, Stanley B Prusiner
Tau prions are thought to aggregate in the central nervous system, resulting in neurodegeneration. Among the tauopathies, Alzheimer's disease (AD) is the most common, whereas argyrophilic grain disease (AGD), corticobasal degeneration (CBD), chronic traumatic encephalopathy (CTE), Pick's disease (PiD), and progressive supranuclear palsy (PSP) are less prevalent. Brain extracts from deceased individuals with PiD, a neurodegenerative disorder characterized by three-repeat (3R) tau prions, were used to infect HEK293T cells expressing 3R tau fused to yellow fluorescent protein (YFP)...
December 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911289/the-brain-s-structural-connectome-mediates-the-relationship-between-regional-neuroimaging-biomarkers-in%C3%A2-alzheimer-s-disease
#19
Sneha Pandya, Amy Kuceyeski, Ashish Raj
Alzheimer's disease (AD), one of the most common causes of dementia in adults, is a progressive neurodegenerative disorder exhibiting well-defined neuropathological hallmarks. It is known that disease pathology involves misfolded amyloid-β (Aβ) and tau proteins, and exhibits a relatively stereotyped progression over decades. The relationship between AD neuropathological hallmarks (Aβ, hypometabolism, and tau proteins) and imaging biomarkers (MRI, AV-45/FDG-PET) is not fully understood. In addition, biomarker pathologies are oftentimes discordant, wherein it may show varying levels of abnormality across brain regions...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/27910931/mutational-analysis-of-prnp-in-alzheimer-s-disease-and-frontotemporal-dementia-in-china
#20
Weiwei Zhang, Bin Jiao, Tingting Xiao, Chuzheng Pan, Xixi Liu, Lin Zhou, Beisha Tang, Lu Shen
The prion protein (PRNP) gene is associated with prion diseases, whereas variants of the PRNP gene may also explain some cases of Alzheimer disease (AD) and frontotemporal dementia (FTD) in Caucasian populations. To determine the prevalence of the PRNP gene in patients with AD and FTD in China, we screened all exons of the PRNP gene in a cohort of 683 cases (606 AD and 77 FTD) in the Chinese Han population and we detected a novel missense mutation p.S17G in a late-onset AD (LOAD) patient. Furthermore, we analyzed the PRNP M/V polymorphism at codon 129, which was previously reported as a risk factor...
December 2, 2016: Scientific Reports
keyword
keyword
80368
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"