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Neurodegenerative disease

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https://www.readbyqxmd.com/read/27906179/pink1-dependent-phosphorylation-of-pink1-and-parkin-is-essential-for-mitochondrial-quality-control
#1
Na Zhuang, Lin Li, She Chen, Tao Wang
Mitochondrial dysfunction has been linked to the pathogenesis of a large number of inherited diseases in humans, including Parkinson's disease, the second most common neurodegenerative disorder. The Parkinson's disease genes pink1 and parkin, which encode a mitochondrially targeted protein kinase, and an E3 ubiquitin ligase, respectively, participate in a key mitochondrial quality-control pathway that eliminates damaged mitochondria. In the current study, we established an in vivo PINK1/Parkin-induced photoreceptor neuron degeneration model in Drosophila with the aim of dissecting the PINK1/Parkin pathway in detail...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27905651/-current-evidence-on-health-benefits-of-the-mediterranean-diet
#2
Catalina Dussaillant, Guadalupe Echeverría, Inés Urquiaga, Nicolás Velasco, Attilio Rigotti
The Mediterranean diet is currently considered a functional diet with an increasing amount of scientific evidence that supports its beneficial effects in human health. Several observational cross-sectional and prospective cohort studies show an association between this diet and a lower prevalence and incidence of chronic diseases, such as cardiovascular disease, cancer, metabolic syndrome, diabetes, and neurodegenerative diseases as well as a reduced overall mortality. Additionally, clinical interventional studies, particularly the PREDIMED (Prevención con Dieta Mediterránea) initiative, have shown, with high quality scientific evidence, that a Mediterranean diet -supplemented either with olive oil or nuts- can lower by 30% the incidence of cardiovascular disease, reverse the metabolic syndrome, and prevent the development of diabetes and aging-related cognitive decline...
August 2016: Revista Médica de Chile
https://www.readbyqxmd.com/read/27905362/-characteristics-of-parkinson-s-disease-course-in-the-heterozygous-carriage-of-mutations-in-the-glucocerebrosidase-a-gene
#3
O A Gan'kina, E E Vasenina, O S Levin, E Yu Fedotova, S N Illarioshkin
Parkinson's disease (PD) is a common neurodegenerative disease. Literature sources indicate the association of PD and mutations in the glucocerebrosidase A (GBA) gene. According to our study, the frequency of the two most common mutations in the GBA gene, N370S and L444P, is 1.85%. Mutation carriers have slower progression of motor symptoms, but are more likely to develop drug-induced motor fluctuations and dyskinesia. In carriers of GBA mutations, the severity of cognitive impairment corresponds to age-matched patients without mutations...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/27905355/-cerebral-microbleeds-in-cerebrovascular-and-neurodegenerative-diseases-with-cognitive-impairment
#4
T A Polyakova, O S Levin
AIM: To study a role of cerebral microbleeds (CMB) in the diagnosis of main cerebrovascular and neurodegenerative diseases with cognitive impairment. MATERIAL AND METHODS: CMB were studied in 120 patients with Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and vascular dementia using 1.5T MRI in T2 * gradient echo. An impact of CMB on cognitive functions and the relationship with signs of vascular and neurodegenerative lesions of the brain were studied as well...
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/27905354/-memantine-in-treatment-of-alzheimer-s-disease-20-years-of-clinical-use
#5
S I Gavrilova
Alzheimer's disease (AD) is a common neurodegenerative disease with progressive course which leads to severe dementia. The author considers the issues of pathogenesis and diagnosis of AD. The efficacy and safety of memantine are analyzed in depth. Recommendations for clinicians on the use of memantine in patients with AD are presented.
2016: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/27905341/heidenhain-variant-of-creutzfeldt-jakob-disease-in-a-patient-who-had-bovine-bioprosthetic-valve-implantation
#6
Jehard Hashoul, Waleed Saliba, Irina Bloch, Haneen Jabaly-Habib
Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disorder characterized by rapidly progressing dementia, general neurologic deterioration, and death. When the leading symptoms are visual disturbances, it is termed as the Heidenhain variant of CJD (HvCJD). CJD was reported following prion-contaminated pericardium transplants but never after bovine bioprosthetic cardiac valve. In this case report, we describe HvCJD in a patient who had a bovine bioprosthetic cardiac valve implant. An 82-year-old-woman was referred to neuro-ophthalmology clinic for unexplained visual loss that started 1 month previously...
October 2016: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/27905268/mapt-mutation-associated-with-frontotemporal-dementia-and-parkinsonism-ftdp-17
#7
Robert Haussmann, Marek Wysocki, Moritz D Brandt, Andreas Hermann, Markus Donix
We present a 56-year-old patient suffering from frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). The history included a three-generation pedigree and the patient was found to be a mutation carrier. The diagnosis was hindered by late appearance of the hypokinetic movement disorder. For clinicians, it is important to consider rare neurodegenerative disease variants in early-onset familial dementia syndromes with behavioral, cognitive, and motor symptoms.
December 1, 2016: International Psychogeriatrics
https://www.readbyqxmd.com/read/27904818/the-government-s-role-in-regulating-coordinating-and-standardizing-the-response-to-alzheimer-s-disease-anticipated-international-cooperation-in-the-area-of-intractable-and-rare-diseases
#8
REVIEW
Qi Tang, Peipei Song, Lingzhong Xu
The World Health Organization (WHO) has emphasized that aging of the population is inextricably linked to many other global public health issues, such as universal health coverage, non-communicable diseases, and disability. However, Alzheimer's Disease International (ADI) estimates that 46.8 million elderly people worldwide were living with dementia in 2015. Alzheimer's disease (AD), the most common form of dementia, is one of the most common neurodegenerative diseases and is the main cause of cognitive impairment...
November 2016: Intractable & Rare Diseases Research
https://www.readbyqxmd.com/read/27904487/tayloring-cell-populations-for-neurodegenerative-diseases
#9
Jeff M Fortin, Loic P Deleyrolle, Brent A Reynolds
No abstract text is available yet for this article.
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27904478/neuro-rejuvenation-for-neuronal-function
#10
REVIEW
Yuan Liu, Richard K Lee
Neurodegenerative eye diseases, such as glaucoma, cause irreversible vision loss in millions of patients worldwide, creating serious medical, economic and social issues. Like other mammalian central nervous system tracts, optic nerve intrinsically lacks the capacity for axonal growth and its surrounding environment is also non-permissive to regeneration. Any axonal damage also triggers a vicious cycle of retinal ganglion cell (RGC) death. Exploring methods that can enhance RGCs survival and promote axonal regeneration will not only enable vision restoration for millions of patients, but also shed light on the treatment of other neurodegenerative diseases...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27904477/axon-injury-induced-endoplasmic-reticulum-stress-and-neurodegeneration
#11
REVIEW
Yang Hu
Injury to central nervous system axons is a common early characteristic of neurodegenerative diseases. Depending on its location and the type of neuron, axon injury often leads to axon degeneration, retrograde neuronal cell death and progressive permanent loss of vital neuronal functions. Although these sequential events are clearly connected, ample evidence indicates that neuronal soma and axon degenerations are active autonomous processes with distinct molecular mechanisms. By exploiting the anatomical and technical advantages of the retinal ganglion cell (RGC)/optic nerve (ON) system, we demonstrated that inhibition of the PERK-eIF2α-CHOP pathway and activation of the X-box binding protein 1 pathway synergistically protect RGC soma and axon, and preserve visual function, in both acute ON traumatic injury and chronic glaucomatous neuropathy...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27904472/clearing-the-corpses-regulatory-mechanisms-novel-tools-and-therapeutic-potential-of-harnessing-microglial-phagocytosis-in-the-diseased-brain
#12
REVIEW
Irune Diaz-Aparicio, Sol Beccari, Oihane Abiega, Amanda Sierra
Apoptosis is a widespread phenomenon that occurs in the brain in both physiological and pathological conditions. Dead cells must be quickly removed to avoid the further toxic effects they exert in the parenchyma, a process executed by microglia, the brain professional phagocytes. Although phagocytosis is critical to maintain tissue homeostasis, it has long been either overlooked or indirectly assessed based on microglial morphology, expression of classical activation markers, or engulfment of artificial phagocytic targets in vitro...
October 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/27903721/cross-talk-between-brain-innate-immunity-and-serotonin-signaling-underlies-depressive-like-behavior-induced-by-alzheimer-s-amyloid-%C3%AE-oligomers-in-mice
#13
Jose Henrique Ledo, Estefania P Azevedo, Danielle Beckman, Felipe C Ribeiro, Luis E Santos, Daniela S Razolli, Grasielle C Kincheski, Helen M Melo, Maria Bellio, Antonio L Teixeira, Licio A Velloso, Debora Foguel, Fernanda G De Felice, Sergio T Ferreira
: Considerable clinical and epidemiological evidence links Alzheimer's disease (AD) and depression. However, the molecular mechanisms underlying this connection are largely unknown. We reported recently that soluble Aβ oligomers (AβOs), toxins that accumulate in AD brains and are thought to instigate synapse damage and memory loss, induce depressive-like behavior in mice. Here, we report that the mechanism underlying this action involves AβO-induced microglial activation, aberrant TNF-α signaling, and decreased brain serotonin levels...
November 30, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27903606/epha2-is-a-functional-receptor-for-the-growth-factor-progranulin
#14
Thomas Neill, Simone Buraschi, Atul Goyal, Catherine Sharpe, Elizabeth Natkanski, Liliana Schaefer, Andrea Morrione, Renato V Iozzo
Although the growth factor progranulin was discovered more than two decades ago, the functional receptor remains elusive. Here, we discovered that EphA2, a member of the large family of Ephrin receptor tyrosine kinases, is a functional signaling receptor for progranulin. Recombinant progranulin bound with high affinity to EphA2 in both solid phase and solution. Interaction of progranulin with EphA2 caused prolonged activation of the receptor, downstream stimulation of mitogen-activated protein kinase and Akt, and promotion of capillary morphogenesis...
November 30, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27903134/o-glcnac-glycosylation-stoichiometry-of-the-fet-protein-family-only-ews-is-glycosylated-with-a-high-stoichiometry
#15
Kazuo Kamemura
Of the FET (fused in sarcoma [FUS]/Ewing sarcoma protein [EWS]/TATA binding protein-associated factor 15 [TAF15]) family of heterogeneous nuclear ribonucleoprotein particle proteins, FUS and TAF15 are consistently and EWS variably found in inclusion bodies in neurodegenerative diseases such as frontotemporal lobar degeneration associated with FUS. It is speculated that dysregulation of FET proteins at the post-translational level is involved in their cytoplasmic deposition. Here, the O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation stoichiometry of the FET proteins was chemoenzymatically analyzed, and it was found that only EWS is dynamically glycosylated with a high stoichiometry in the neural cell lines tested and in mouse brain...
December 1, 2016: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/27902765/loss-of-cathepsin-b-and-l-leads-to-lysosomal-dysfunction-npc-like-cholesterol-sequestration-and-accumulation-of-the-key-alzheimer-s-proteins
#16
Stjepko Cermak, Marko Kosicek, Aleksandra Mladenovic-Djordjevic, Kosara Smiljanic, Selma Kanazir, Silva Hecimovic
Proper function of lysosomes is particularly important in neurons, as they cannot dilute accumulated toxic molecules and aggregates by cell division. Thus, impairment of lysosomal function plays an important role in neuronal degeneration and in the pathogenesis of numerous neurodegenerative diseases. In this work we analyzed how inhibition and/or loss of the major lysosomal proteases, the cysteine cathepsins B and L (CtsB/L), affects lysosomal function, cholesterol metabolism and degradation of the key Alzheimer's disease (AD) proteins...
2016: PloS One
https://www.readbyqxmd.com/read/27902447/a-unique-type-of-gsk-3-inhibitor-brings-new-opportunities-to-the-clinic
#17
Avital Licht-Murava, Rom Paz, Lilach Vaks, Limor Avrahami, Batya Plotkin, Miriam Eisenstein, Hagit Eldar-Finkelman
Development of protein kinase inhibitors is a focus of many drug discovery programs. A major problem, however, is the limited specificity of the commonly used adenosine triphosphate-competitive inhibitors and the weak inhibition of the more selective substrate-competitive inhibitors. Glycogen synthase kinase-3 (GSK-3) is a promising drug target for treating neurodegenerative disorders, including Alzheimer's disease (AD), but most GSK-3 inhibitors have not reached the clinic. We describe a new type of GSK-3 inhibitor, L807mts, that acts through a substrate-to-inhibitor conversion mechanism that occurs within the catalytic site of the enzyme...
November 15, 2016: Science Signaling
https://www.readbyqxmd.com/read/27902446/science-signaling-podcast-for-15-november-2016-a-new-type-of-kinase-inhibitor
#18
Hagit Eldar-Finkelman, Annalisa M VanHook
This Podcast features an interview with Hagit Eldar-Finkelman, author of a Research Article that appears in the 15 November 2016 issue of Science Signaling, about a newly developed inhibitor of glycogen synthase kinase 3 (GSK-3). GSK-3 participates in several signaling networks and has been implicated in various pathologies, including neurodegenerative diseases, cognitive impairments, and cancer. Licht-Murava et al developed L807mts, a substrate-competitive peptide inhibitor that blocks GSK-3 activity through an unusual mechanism...
November 15, 2016: Science Signaling
https://www.readbyqxmd.com/read/27901468/loss-of-frataxin-activates-the-iron-sphingolipid-pdk1-mef2-pathway-in-mammals
#19
Kuchuan Chen, Tammy Szu-Yu Ho, Guang Lin, Kai Li Tan, Matthew N Rasband, Hugo J Bellen
Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by mutations in Frataxin (FXN). Loss of FXN causes impaired mitochondrial function and iron homeostasis. An elevated production of reactive oxygen species (ROS) was previously proposed to contribute to the pathogenesis of FRDA. We recently showed that loss of frataxin homolog (fh), a Drosophila homolog of FXN, causes a ROS independent neurodegeneration in flies (Chen et al., 2016). In fh mutants, iron accumulation in the nervous system enhances the synthesis of sphingolipids, which in turn activates 3-phosphoinositide dependent protein kinase-1 (Pdk1) and myocyte enhancer factor-2 (Mef2) to trigger neurodegeneration of adult photoreceptors...
November 30, 2016: ELife
https://www.readbyqxmd.com/read/27900887/toward-modeling-the-human-nervous-system-in-a-dish-recent-progress-and-outstanding-challenges
#20
Barbora Vagaska, Patrizia Ferretti
Studying the cellular and molecular bases governing development, and normal and abnormal functions of the human CNS is hampered by its complexity and the very limited possibility of experimentally manipulating it in vivo. Development of 3D, tissue-like culture systems offers much promise for boosting our understanding of human neural development, birth defects, neurodegenerative diseases and neural injury, and for providing platforms that will more accurately predict efficacy of putative therapeutic compounds and assess responses to potentially neurotoxic agents...
November 30, 2016: Regenerative Medicine
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