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https://www.readbyqxmd.com/read/28527219/tmem230-accumulation-in-granulovacuolar-degeneration-bodies-and-dystrophic-neurites-of-alzheimer-s-disease
#1
Sandra L Siedlak, Yingfei Jiang, Mikayla L Huntley, Luwen Wang, Ju Gao, Fei Xie, Jingyi Liu, Bo Su, George Perry, Xinglong Wang
Transmembrane Protein 230 (TMEM230) is a newly identified protein associated with Parkinson's disease (PD) found in Lewy bodies and Lewy neurites of patients with PD or dementia with Lewy body disease. However, TMEM230 has not yet been investigated in the most common neurodegenerative disorder, Alzheimer's disease (AD). Here, we demonstrate that the expression of TMEM230 is specifically increased in neurons in AD patients. Importantly, both granulovacuolar degeneration (GVD) and dystrophic neurites (DNs), two prominent characteristic pathological structures associated with AD, contain TMEM230 aggregates...
May 17, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28527044/endocytic-vesicle-rupture-is-a-conserved-mechanism-of-cellular-invasion-by-amyloid-proteins
#2
William P Flavin, Luc Bousset, Zachary C Green, Yaping Chu, Stratos Skarpathiotis, Michael J Chaney, Jeffrey H Kordower, Ronald Melki, Edward M Campbell
Numerous pathological amyloid proteins spread from cell to cell during neurodegenerative disease, facilitating the propagation of cellular pathology and disease progression. Understanding the mechanism by which disease-associated amyloid protein assemblies enter target cells and induce cellular dysfunction is, therefore, key to understanding the progressive nature of such neurodegenerative diseases. In this study, we utilized an imaging-based assay to monitor the ability of disease-associated amyloid assemblies to rupture intracellular vesicles following endocytosis...
May 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28522732/unbiased-proteomics-of-early-lewy-body-formation-model-implicates-active-microtubule-affinity-regulating-kinases-marks-in-synucleinopathies
#3
Michael X Henderson, Charlotte Hiu-Yan Chung, Dawn M Riddle, Bin Zhang, Ronald J Gathagan, Steven H Seeholzer, John Q Trojanowski, Virginia M Y Lee
Parkinson's disease (PD) patients progressively accumulate intracytoplasmic inclusions formed by misfolded α-synuclein known as Lewy bodies (LBs). LBs also contain other proteins that may or may not be relevant in the disease process. To identify proteins involved early in LB formation, we performed proteomic analysis of insoluble proteins in a primary neuron culture model of α-synuclein pathology. We identified proteins previously found in authentic LBs in PD as well as several novel proteins, including the microtubule affinity-regulating kinase 1 (MARK1), one of the most enriched proteins in this model of LB formation...
May 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28516990/cross-talk-between-neurometals-and-amyloidogenic-proteins-at-the-synapse-and-the-pathogenesis-of-neurodegenerative-diseases
#4
REVIEW
M Kawahara, M Kato-Negishi, K Tanaka
Increasing evidence suggests that disruption of metal homeostasis contributes to the pathogenesis of various neurodegenerative diseases, including Alzheimer's disease, prion diseases, Lewy body diseases, and vascular dementia. Conformational changes of disease-related proteins (amyloidogenic proteins), such as β-amyloid protein, prion proteins, and α-synuclein, are well-established contributors to neurotoxicity and to the pathogenesis of these diseases. Recent studies have demonstrated that these amyloidogenic proteins are metalloproteins that bind trace elements, including zinc, iron, copper, and manganese, and play significant roles in the maintenance of metal homeostasis...
May 18, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28516276/p2x7-receptor-pannexin-1-interaction-mediates-extracellular-alpha-synuclein-induced-atp-release-in-neuroblastoma-sh-sy5y-cells
#5
Anna Wilkaniec, Magdalena Gąssowska, Grzegorz A Czapski, Magdalena Cieślik, Grzegorz Sulkowski, Agata Adamczyk
Abnormalities of alpha-synuclein (ASN), the main component of protein deposits (Lewy bodies), were observed in Parkinson's disease (PD), dementia with Lewy bodies, Alzheimer's disease, and other neurodegenerative disorders. These alterations include increase in the levels of soluble ASN oligomers in the extracellular space. Numerous works have identified several mechanisms of their toxicity, including stimulation of the microglial P2X7 receptor leading to oxidative stress. While the significant role of purinergic signaling-particularly, P2 family receptors-in neurodegenerative disorders is well known, the interaction of extracellular soluble ASN with neuronal purinergic receptors is yet to be studied...
May 17, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28516219/decreased-sensory-nerve-excitation-and-bone-pain-associated-with-mouse-lewis-lung-cancer-in-trpv1-deficient-mice
#6
Hiroki Wakabayashi, Satoshi Wakisaka, Toru Hiraga, Kenji Hata, Riko Nishimura, Makoto Tominaga, Toshiyuki Yoneda
Bone pain is one of the most common and life-limiting complications of cancer metastasis to bone. Although the mechanism of bone pain still remains poorly understood, bone pain is evoked as a consequence of sensitization and excitation of sensory nerves (SNs) innervating bone by noxious stimuli produced in the microenvironment of bone metastases. We showed that bone is innervated by calcitonin gene-related protein (CGRP)(+) SNs extending from dorsal root ganglia (DRG), the cell body of SNs, in mice. Mice intratibially injected with Lewis lung cancer (LLC) cells showed progressive bone pain evaluated by mechanical allodynia and flinching with increased CGRP(+) SNs in bone and augmented SN excitation in DRG as indicated by elevated numbers of pERK- and pCREB-immunoreactive neurons...
May 17, 2017: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/28515269/effect-of-omega-3-supplementation-on-neuropathy-in-type-1-diabetes-a-12-month-pilot-trial
#7
Evan J H Lewis, Bruce A Perkins, Leif E Lovblom, Richard P Bazinet, Thomas M S Wolever, Vera Bril
OBJECTIVE: To test the hypothesis that 12 months of seal oil omega-3 polyunsaturated fatty acids (ω-3 PUFA) supplementation will stop the known progression of diabetic sensorimotor polyneuropathy (DSP) in type 1 diabetes mellitus (T1DM). METHODS: Individuals with T1DM and evidence of DSP as determined by a Toronto Clinical Neuropathy Score ≥1 were recruited to participate in a single-arm, open-label trial of seal oil ω-3 PUFA supplementation (10 mL·d(-1); 750 mg eicosapentaenoic acid, 560 mg docosapentaenoic acid, and 1,020 mg docosahexaenoic acid) for 1 year...
May 17, 2017: Neurology
https://www.readbyqxmd.com/read/28515265/clinical-marker-for-alzheimer-disease-pathology-in-logopenic-primary-progressive-aphasia
#8
Lucia A A Giannini, David J Irwin, Corey T McMillan, Sharon Ash, Katya Rascovsky, David A Wolk, Vivianna M Van Deerlin, Edward B Lee, John Q Trojanowski, Murray Grossman
OBJECTIVE: To determine whether logopenic features of phonologic loop dysfunction reflect Alzheimer disease (AD) neuropathology in primary progressive aphasia (PPA). METHODS: We performed a retrospective case-control study of 34 patients with PPA with available autopsy tissue. We compared baseline and longitudinal clinical features in patients with primary AD neuropathology to those with primary non-AD pathologies. We analyzed regional neuroanatomic disease burden in pathology-defined groups using postmortem neuropathologic data...
May 17, 2017: Neurology
https://www.readbyqxmd.com/read/28514599/a-bioenergetics-systems-evaluation-of-ketogenic-diet-liver-effects
#9
Lewis J Hutfles, Heather M Wilkins, Scott J Koppel, Ian W Weidling, J Eva Selfridge, Eephie Tan, John P Thyfault, Chad Slawson, Aron W Fenton, Hao Zhu, Russell H Swerdlow
Ketogenic diets induce hepatocyte fatty acid oxidation and ketone body production. To further evaluate how ketogenic diets affect hepatocyte bioenergetic infrastructure, we analyzed livers from C57Bl/6J male mice maintained for one month on a ketogenic or standard chow diet. Compared to the standard diet, the ketogenic diet increased cytosolic and mitochondrial protein acetylation and also altered protein succinylation patterns. SIRT3 protein decreased while SIRT5 protein increased, and gluconeogenesis, oxidative phosphorylation, and mitochondrial biogenesis pathway proteins were variably and likely strategically altered...
May 17, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28513079/rem-sleep-behavior-disorder-in-parkinson-s-disease-and-other-synucleinopathies
#10
REVIEW
Erik K St Louis, Angelica R Boeve, Bradley F Boeve
Rapid eye movement sleep behavior disorder is characterized by dream enactment and complex motor behaviors during rapid eye movement sleep and rapid eye movement sleep atonia loss (rapid eye movement sleep without atonia) during polysomnography. Rapid eye movement sleep behavior disorder may be idiopathic or symptomatic and in both settings is highly associated with synucleinopathy neurodegeneration, especially Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure...
May 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28505261/survival-and-causes-of-death-among-people-with-clinically-diagnosed-synucleinopathies-with-parkinsonism-a-population-based-study
#11
Rodolfo Savica, Brandon R Grossardt, James H Bower, J Eric Ahlskog, Bradley F Boeve, Jonathan Graff-Radford, Walter A Rocca, Michelle M Mielke
Importance: To our knowledge, a comprehensive study of the survival and causes of death of persons with synucleinopathies compared with the general population has not been conducted. Understanding the long-term outcomes of these conditions may inform patients and caregivers of the expected disease duration and may help with care planning. Objective: To compare survival rates and causes of death among patients with incident, clinically diagnosed synucleinopathies and age- and sex-matched referent participants...
May 15, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28504037/plasma-butyrylcholinesterase-activity-a-possible-biomarker-for-differential-diagnosis-between-alzheimer-s-disease-and-dementia-with-lewy-bodies
#12
N D Josviak, M S Batistela, R K M Souza, N R Wegner, G F Bono, C D Sulzbach, D P Simão-Silva, M R Piovezan, R L R Souza, L Furtado-Alle
Butyrylcholinesterase (BChE) is an enzyme encoded by BCHE gene, responsible for catalyzing the hydrolysis of acetylcholine. K and -116A BCHE variants were associated with decrease in plasma BChE activity, and their influence has been investigated in diseases with a cholinergic deficit such as Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). In order to check the influence of BCHE genetic variants on enzymatic activity, all patients and controls were genotyped for K and -116A variants. We found lower plasma BChE activity in DLB patients compared to elderly controls and to AD independent of the presence of K or -116A variants...
May 15, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/28502507/impact-of-bariatric-surgery-on-apolipoprotein-c-iii-levels-and-lipoprotein-distribution-in-obese-human-subjects
#13
Marie Maraninchi, Nadège Padilla, Sophie Béliard, Bruno Berthet, Juan-Patricio Nogueira, Jeanine Dupont-Roussel, Julien Mancini, Audrey Bégu-Le Corroller, Noémie Dubois, Rachel Grangeot, Catherine Mattei, Marion Monclar, Anastasia Calabrese, Carole Guérin, Charles Desmarchelier, Alain Nicolay, Changting Xiao, Patrick Borel, Gary F Lewis, René Valéro
BACKGROUND: Elevated apolipoprotein C-III (apoC-III) has been postulated to contribute to the atherogenic dyslipidemia seen in obesity and insulin-resistant states, mainly by impairing plasma triglyceride-rich lipoprotein (TRL) metabolism. Bariatric surgery is associated with improvements of several obesity-associated metabolic abnormalities, including a reduction in plasma triglycerides (TGs) and an increase in plasma high-density lipoprotein cholesterol (HDL-C). OBJECTIVES: We investigated the specific effect of bariatric surgery on apoC-III concentrations in plasma, non-HDL, and HDL fractions in relation to lipid profile parameters evolution...
March 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28499012/resistance-to-alzheimer-disease-neuropathologic-changes-and-apparent-cognitive-resilience-in-the-nun-and-honolulu-asia-aging-studies
#14
Caitlin S Latimer, C Dirk Keene, Margaret E Flanagan, Laura S Hemmy, Kelvin O Lim, Lon R White, Kathleen S Montine, Thomas J Montine
Two population-based studies key to advancing knowledge of brain aging are the Honolulu-Asia Aging Study (HAAS) and the Nun Study. Harmonization of their neuropathologic data allows cross comparison, with findings common to both studies likely generalizable, while distinct observations may point to aging brain changes that are dependent on sex, ethnicity, environment, or lifestyle factors. Here, we expanded the neuropathologic evaluation of these 2 studies using revised NIA-Alzheimer's Association guidelines and compared directly the neuropathologic features of resistance and apparent cognitive resilience...
June 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28495859/alpha-synuclein-may-cross-bridge-v-snare-and-acidic-phospholipids-to-facilitate-snare-dependent-vesicle-docking
#15
Xiaochu Lou, Jaewook Kim, Brenden J Hawk, Yeon-Kyun Shin
Misfolded α-synuclein/A-syn is widely recognized as primal cause of neurodegenerative diseases including Parkinson's and dementia with Lewy bodies. The normal cellular function of A-syn has however been elusive. There is evidence that A-syn plays a variety of roles in the exocytotic pathway in the neuron, but the underlying molecular mechanisms are unclear. A-syn has been known to interact with negatively charged phospholipids and with vesicle SNARE protein VAMP2 as well. Using single vesicle-vesicle docking/fusion assays, we find that A-syn promotes SNARE-dependent vesicles docking significantly at 2...
May 11, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28493205/development-of-the-life-impact-burn-recovery-evaluation-libre-profile-assessing-burn-survivors-social-participation
#16
Lewis E Kazis, Molly Marino, Pengsheng Ni, Marina Soley Bori, Flor Amaya, Emily Dore, Colleen M Ryan, Jeff C Schneider, Vivian Shie, Amy Acton, Alan M Jette
PURPOSE: Measuring the impact burn injuries have on social participation is integral to understanding and improving survivors' quality of life, yet there are no existing instruments that comprehensively measure the social participation of burn survivors. This project aimed to develop the Life Impact Burn Recovery Evaluation Profile (LIBRE), a patient-reported multidimensional assessment for understanding the social participation after burn injuries. METHODS: 192 questions representing multiple social participation areas were administered to a convenience sample of 601 burn survivors...
May 10, 2017: Quality of Life Research
https://www.readbyqxmd.com/read/28491896/physical-activity-predicts-reduced-plasma-%C3%AE-amyloid-in-the-cardiovascular-health-study
#17
Chelsea M Stillman, Oscar L Lopez, James T Becker, Lewis H Kuller, Pankaj D Mehta, Russell P Tracy, Kirk I Erickson
OBJECTIVE: Higher levels of physical activity (PA) reduce the risk of cognitive impairment, but the underlying mechanisms are unclear. Using longitudinal data from the Cardiovascular Health Study, we examined whether PA predicted plasma Aβ levels and risk for cognitive decline 9-13 years later. METHODS: Linear and logistic regressions (controlling for APOE status, age, gender, body mass index, cardiovascular disease, brain white matter lesions, and cystatin C levels) tested associations between PA, Aβ, and cognitive impairment in a sample of 149 cognitively normal older adults (mean age 83 years)...
May 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28490314/pain-experience-in-dementia-subtypes-a-systematic-review
#18
Tarik T Binnekade, Janime Van Kooten, Frank Lobbezoo, Didi Rhebergen, J C Van der Wouden, Martin Smalbrugge, Erik J A Scherder
Recently, the number of studies focusing on pain in dementia has increased considerably. Still, little attention has been paid to the influence of the neuropathology of different dementia subtypes on pain experience. In 2003, a review identified several studies that indicated a relation between dementia subtype and pain experience. Now, ten years later, an update is warranted. We conducted a systematic review to identify studies that assessed pain experience and dementia subtypes by searching PubMed, Embase, PsycINFO, CINAHL, and Cochrane Library...
2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28488154/impact-of-multiple-pathologies-on-the-threshold-for-clinically-overt-dementia
#19
REVIEW
Alifiya Kapasi, Charles DeCarli, Julie A Schneider
Longitudinal clinical-pathological studies have increasingly recognized the importance of mixed pathologies (the coexistence of one or more neurodegenerative and cerebrovascular disease pathologies) as important factors in the development of Alzheimer's disease (AD) and other forms of dementia. Older persons with AD pathology, often have concomitant cerebrovascular disease pathologies (macroinfarcts, microinfarcts, atherosclerosis, arteriolosclerosis, cerebral amyloid angiopathy) as well as other concomitant neurodegenerative disease pathologies (Lewy bodies, TDP-43, hippocampal sclerosis)...
May 9, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28487947/high-expression-levels-of-the-d686n-parkinson-s-disease-mutation-in-vps35-induces-%C3%AE-synuclein-dependent-toxicity-in-yeast
#20
Yi Huang, Xiang Chen, Xiaofei He, Caifeng Guo, Xicui Sun, Fengyin Liang, Simei Long, Xilin Lu, Luyang Feng, Wenyuan Guo, Yixuan Zeng, Zhong Pei
Parkinson's disease (PD) is a common neurodegenerative disorder that affects ~2% of the human population aged >65. α‑synuclein serves a role in the pathogenesis of PD as it is a primary component of Lewy bodies, a pathological feature of PD. Endosomal‑lysosomal dysfunction may be a key factor involved in the pathophysiology of PD, and may cause PD‑associated neurodegeneration via α‑synuclein‑dependent and ‑independent mechanisms. The D620N mutation in the endosomal‑lysosomal gene, vacuolar protein sorting‑associated protein 35 (VPS35), has been linked to PD...
May 9, 2017: Molecular Medicine Reports
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