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https://www.readbyqxmd.com/read/29926816/natural-polyphenols-effects-on-protein-aggregates-in-alzheimer-s-and-parkinson-s-prion-like-diseases
#1
REVIEW
Aline Freyssin, Guylène Page, Bernard Fauconneau, Agnès Rioux Bilan
Alzheimer's and Parkinson's diseases are the most common neurodegenerative diseases. They are characterized by protein aggregates and so can be considered as prion-like disease. The major components of these deposits are amyloid peptide and tau for Alzheimer's disease, α-synuclein and synphilin-1 for Parkinson's disease. Drugs currently proposed to treat these pathologies do not prevent neurodegenerative processes and are mainly symptomatic therapies. Molecules inducing inhibition of aggregation or disaggregation of these proteins could have beneficial effects, especially if they have other beneficial effects for these diseases...
June 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29924993/single-molecule-characterization-of-the-interactions-between-extracellular-chaperones-and-toxic-%C3%AE-synuclein-oligomers
#2
Daniel R Whiten, Dezerae Cox, Mathew H Horrocks, Christopher G Taylor, Suman De, Patrick Flagmeier, Laura Tosatto, Janet R Kumita, Heath Ecroyd, Christopher M Dobson, David Klenerman, Mark R Wilson
The aberrant aggregation of α-synuclein is associated with several human diseases, collectively termed the α-synucleinopathies, which includes Parkinson's disease. The progression of these diseases is, in part, mediated by extracellular α-synuclein oligomers that may exert effects through several mechanisms, including prion-like transfer, direct cytotoxicity, and pro-inflammatory actions. In this study, we show that two abundant extracellular chaperones, clusterin and α2 -macroglobulin, directly bind to exposed hydrophobic regions on the surface of α-synuclein oligomers...
June 19, 2018: Cell Reports
https://www.readbyqxmd.com/read/29923311/primary-tissue-for-cellular-brain-repair-in-parkinson-s-disease-promise-problems-and-the-potential-of-biomaterials
#3
Niamh Moriarty, Clare L Parish, Eilís Dowd
The dopamine precursor, levodopa, remains the 'gold-standard' treatment for Parkinson's disease, and, although it provides superlative efficacy in the early stages of the disease, its long-term use is limited by the development of severe motor side effects and a significant abating of therapeutic efficacy. Therefore, there remains a major unmet clinical need for the development of effective neuroprotective, neurorestorative or neuroreparatory therapies for this condition. The relatively selective loss of dopaminergic neurons from the nigrostriatal pathway makes Parkinson's disease an ideal candidate for reparative cell therapies wherein the dopaminergic neurons that are lost in the condition are replaced through direct cell transplantation into the brain...
June 20, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29920069/modulating-protein-phosphatase-2a-rescues-disease-phenotype-in-neurodegenerative-tauopathies
#4
Simon McKenzie-Nickson, Jacky Chan, Keyla Perez, Lin W Hung, Lesley Cheng, Amelia Sedjahtera, Lydia Gunawan, Paul A Adlard, David J Hayne, Lachlan E Mcinnes, Paul S Donnelly, David I Finkelstein, Professor Andrew Hill, Kevin J Barnham
Alzheimer's disease (AD) is the leading cause of dementia worldwide accounting around 70% of all cases. There is currently no treatment for AD beyond symptom management and attempts at developing disease-modifying therapies have yielded very little. These strategies have traditionally targeted the peptide Aβ which is thought to drive pathology. However, the lack of clinical translation of these Aβ-centric strategies underscores the need for diverse treatment strategies targeting other aspects of the disease...
June 19, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29916567/-chronic-diseases-in-neuromotor-rehabilitation-medicine
#5
Antonio Nardone, Elena Paola Ferrari
OBJECTIVES: Chronic diseases are a major problem, whose importance is nowadays raising up. Up to 86% of deaths are directly related to chronic diseases in Europe as they represent large amount of total diseases, with a major impact on global health spending. METHODS: Patients suffering from heterogeneous disabilities (such as Parkinson's disease, stroke, multiple sclerosis, osteoporosis, osteoarthritis) often show an interaction between the main disease and comorbidity and multimorbidity...
February 2018: Giornale Italiano di Medicina del Lavoro Ed Ergonomia
https://www.readbyqxmd.com/read/29910724/cdk5-inhibitory-peptide-prevents-loss-of-dopaminergic-neurons-and-alleviates-behavioral-changes-in-an-mptp-induced-parkinson-s-disease-mouse-model
#6
Rongni He, Wei Huang, Yaowei Huang, Miaojing Xu, Pingping Song, Yinwei Huang, Huifang Xie, Yafang Hu
Parkinson's disease (PD) is one of the most affected neurodegenerative diseases in the world. Deregulation of cyclin-dependent kinase 5 (Cdk5) is believed to play an important role in neurodegenerative diseases including PD. p25 is a cleavage peptide of p35, a physiologic activator of Cdk5. p25 combines to Cdk5 and leads to the hyperactivity of Cdk5, which in turn hyperphosphorylates downstream substrates and leads to neuroinflammation and apoptosis of neurons. Previously, we have demonstrated that adeno-associated virus serotype-9 (AAV9) mediated Cdk5 inhibitory peptide (CIP) inhibits the activity of Cdk5/p25 complex and alleviates pathologic and behavioral changes in Alzheimer's disease mouse model...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29907159/jnk-mediated-microglial-dicer-degradation-potentiates-inflammatory-responses-to-induce-dopaminergic-neuron-loss
#7
Qing Wang, Qian He, Yifei Chen, Wei Shao, Chao Yuan, Yizheng Wang
BACKGROUND: Amplified inflammation is important for the progression of Parkinson's disease (PD). However, how this enhanced inflammation is regulated remains largely unknown. Deletion of DICER leads to progressive dopamine neuronal loss and induces gliosis. We hypothesized that the homeostasis of microglial DICER would be responsible for the amplified inflammation in the mouse model of PD. METHODS: The microglia or C57BL/6 mice were treated or injected with l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium (MPP+ ), respectively, for the model establishment...
June 15, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29906474/acteoside-protects-against-6-ohda-induced-dopaminergic-neuron-damage-via-nrf2-are-signaling-pathway
#8
Maiquan Li, Fei Zhou, Tao Xu, Huaxin Song, Baiyi Lu
Acteoside has been reported to have antioxidant and neuroprotective effect, which is a promising therapeutic way in prevention and treatment of Parkinson's disease. The present study was aimed to understand the neuroprotective effect of acteoside and to elucidate its underlying mechanism. 6-hydroxydopamine (6-OHDA)-induced neural damage in zebrafish model was used to study the protective effect of acteoside on Parkinson disease (PD). Locomotion behavioral test showed that acteoside could prevent 6-OHDA-stimulated movement disorders...
June 12, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29902695/therapeutic-strategies-for-targeting-neurodegenerative-protein-misfolding-disorders
#9
REVIEW
Robert H Scannevin
Neurodegenerative diseases can arise from a multitude of different pathological drivers, however protein misfolding appears to be a common molecular feature central to several disorders. Protein folding, and attainment of correct secondary and tertiary structure, is essential for proper protein function. Protein misfolding gives rise to structural perturbations that can result in loss of protein function or a gain of toxic function, such as through aggregation, either of which can initiate and propagate biological responses that are deleterious to cells...
June 11, 2018: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29897434/the-c-abl-inhibitor-radotinib-hcl-is-neuroprotective-in-a-preclinical-parkinson-s-disease-mouse-model
#10
Saebom Lee, Sangjune Kim, Yong Joo Park, Seung Pil Yun, Seung-Hwan Kwon, Donghoon Kim, Dong Yeon Kim, Jae Soo Shin, Dae Jin Cho, Gong Yeal Lee, Hyun Soo Ju, Hyo Jung Yun, Jae Hong Park, Wonjoong Richard Kim, Eun Ah Jung, Seulki Lee, Han Seok Ko
Accumulating evidence suggests that the nonreceptor tyrosine kinase c-Abl plays an important role in the progression of Parkinson's disease (PD) and c-Abl inhibition could be neuroprotective in PD and related α-synucleinopathies. Nilotinib, a c-Abl inhibitor, has shown improved motor and cognitive symptoms in PD patients. However, issues concerning blood-brain barrier (BBB) penetration, lack of selectivity, and safety still remain. Radotinib HCl is a selective Bcr-Abl kinase inhibitor that not only effectively access the brain, but also exhibits greater pharmacokinetic properties and safety profiles compared to Nilotinib and other c-Abl inhibitors...
April 20, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29895861/%C3%AE-synuclein-oligomers-interact-with-atp-synthase-and-open-the-permeability-transition-pore-in-parkinson-s-disease
#11
Marthe H R Ludtmann, Plamena R Angelova, Mathew H Horrocks, Minee L Choi, Margarida Rodrigues, Artyom Y Baev, Alexey V Berezhnov, Zhi Yao, Daniel Little, Blerida Banushi, Afnan Saleh Al-Menhali, Rohan T Ranasinghe, Daniel R Whiten, Ratsuda Yapom, Karamjit Singh Dolt, Michael J Devine, Paul Gissen, Tilo Kunath, Morana Jaganjac, Evgeny V Pavlov, David Klenerman, Andrey Y Abramov, Sonia Gandhi
Protein aggregation causes α-synuclein to switch from its physiological role to a pathological toxic gain of function. Under physiological conditions, monomeric α-synuclein improves ATP synthase efficiency. Here, we report that aggregation of monomers generates beta sheet-rich oligomers that localise to the mitochondria in close proximity to several mitochondrial proteins including ATP synthase. Oligomeric α-synuclein impairs complex I-dependent respiration. Oligomers induce selective oxidation of the ATP synthase beta subunit and mitochondrial lipid peroxidation...
June 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29892785/mediterranean-diet-in-preventing-neurodegenerative-diseases
#12
REVIEW
Hannah Gardener, Michelle R Caunca
PURPOSE OF REVIEW: We reviewed the most recent literature examining the associations between the Mediterranean-style diet (MD), neurodegenerative diseases, and markers and mechanisms of neurodegeneration. RECENT FINDINGS: Most, but not all, epidemiologic studies report a protective association between MD adherence, cognitive impairment, and brain health. Data from clinical trials supporting these observational findings are also emerging. Limited evidence suggests that MD adherence may be protective for Parkinson's disease risk...
March 2018: Current Nutrition Reports
https://www.readbyqxmd.com/read/29892066/block-of-a1-astrocyte-conversion-by-microglia-is-neuroprotective-in-models-of-parkinson-s-disease
#13
Seung Pil Yun, Tae-In Kam, Nikhil Panicker, SangMin Kim, Yumin Oh, Jong-Sung Park, Seung-Hwan Kwon, Yong Joo Park, Senthilkumar S Karuppagounder, Hyejin Park, Sangjune Kim, Nayeon Oh, Nayoung Alice Kim, Saebom Lee, Saurav Brahmachari, Xiaobo Mao, Jun Hee Lee, Manoj Kumar, Daniel An, Sung-Ung Kang, Yunjong Lee, Kang Choon Lee, Dong Hee Na, Donghoon Kim, Sang Hun Lee, Viktor V Roschke, Shane A Liddelow, Zoltan Mari, Ben A Barres, Valina L Dawson, Seulki Lee, Ted M Dawson, Han Seok Ko
Activation of microglia by classical inflammatory mediators can convert astrocytes into a neurotoxic A1 phenotype in a variety of neurological diseases1,2 . Development of agents that could inhibit the formation of A1 reactive astrocytes could be used to treat these diseases for which there are no disease-modifying therapies. Glucagon-like peptide-1 receptor (GLP1R) agonists have been indicated as potential neuroprotective agents for neurologic disorders such as Alzheimer's disease and Parkinson's disease3-13 ...
June 11, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29889613/a-comparative-study-of-stabilizing-effect-and-antioxidant-activity-of-different-antioxidants-on-levodopa-loaded-liposomes
#14
Elena García Esteban, María José Cózar-Bernal, Antonio M Rabasco Álvarez, María Luisa González-Rodríguez
The aim of this study was to evaluate the stability of levodopa liposomes co-loaded with three different antioxidants (curcumin, ascorbic acid and superoxide dismutase (SOD)). For this purpose, multilamellar liposomes were prepared. Curcumin was added into the lipid bilayer while ascorbic acid and SOD were placed into the aqueous phase. The influence of preparation technique and surface charge were also investigated. Vesicles were characterized and free radical scavenging potential was determined. From stability study, ascorbic acid showed better stabilizing effect...
June 11, 2018: Journal of Microencapsulation
https://www.readbyqxmd.com/read/29888323/circulating-neurotoxic-5-ht2a-receptor-agonist-autoantibodies-in-adult-type-2-diabetes-with-parkinson-s-disease
#15
Mark B Zimering
Aims: To test whether circulating neurotoxic autoantibodies increase in adult type 2 diabetes mellitus with Parkinson's disease (PD) or dementia. To identify the G-protein coupled receptor on neuroblastoma cells mediating neural inhibitory effects in diabetic Parkinson's disease plasma autoantibodies. To determine the mechanism of accelerated neuroblastoma cell death and acute neurite retraction induced by diabetic Parkinson's disease and dementia autoantibodies. Methods: Protein-A eluates from plasma of twelve older adult male diabetic patients having Parkinson's disease (n=10) or dementia (n=2), and eight age-matched control diabetic patients were tested for ability to cause accelerated N2A neuroblastoma cell death and acute neurite retraction...
2018: Journal of Endocrinology and Diabetes
https://www.readbyqxmd.com/read/29882776/the-role-of-magnesium-in-neurological-disorders
#16
REVIEW
Anna E Kirkland, Gabrielle L Sarlo, Kathleen F Holton
Magnesium is well known for its diverse actions within the human body. From a neurological standpoint, magnesium plays an essential role in nerve transmission and neuromuscular conduction. It also functions in a protective role against excessive excitation that can lead to neuronal cell death (excitotoxicity), and has been implicated in multiple neurological disorders. Due to these important functions within the nervous system, magnesium is a mineral of intense interest for the potential prevention and treatment of neurological disorders...
June 6, 2018: Nutrients
https://www.readbyqxmd.com/read/29876284/the-site-of-stimulation-moderates-neuropsychiatric-symptoms-after-subthalamic-deep-brain-stimulation-for-parkinson-s-disease
#17
Philip E Mosley, David Smith, Terry Coyne, Peter Silburn, Michael Breakspear, Alistair Perry
Deep brain stimulation of the subthalamic nucleus for Parkinson's disease is an established advanced therapy that addresses motor symptoms and improves quality of life. However, it has also been associated with neuropsychiatric symptoms such as impulsivity and hypomania. When significant, these symptoms can be distressing, necessitating psychiatric intervention. However, a comprehensive analysis of neurocognitive and neuropsychiatric outcomes with reference to the site of subthalamic stimulation has not been undertaken...
2018: NeuroImage: Clinical
https://www.readbyqxmd.com/read/29876138/intracerebroventricular-administration-of-l-arginine-improves-spatial-memory-acquisition-in-triple-transgenic-mice-via-reduction-of-oxidative-stress-and-apoptosis
#18
Gennadiy Fonar, Baruh Polis, Tomer Meirson, Alexander Maltsev, Evan Elliott, Abraham O Samson
Arginine is one of the most versatile semi-essential amino acids. Further to the primary role in protein biosynthesis, arginine is involved in the urea cycle, and it is a precursor of nitric oxide. Arginine deficiency is associated with neurodegenerative diseases such as Parkinson's, Huntington's and Alzheimer's diseases (AD). In this study, we administer arginine intracerebroventricularly in a murine model of AD and evaluate cognitive functions in a set of behavioral tests. In addition, the effect of arginine on synaptic plasticity was tested electrophysiologically by assessment of the hippocampal long-term potentiation (LTP)...
2018: Translational Neuroscience
https://www.readbyqxmd.com/read/29875659/multi-target-protective-effects-of-gintonin-in-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-mediated-model-of-parkinson-s-disease-via-lysophosphatidic-acid-receptors
#19
Jong Hee Choi, Minhee Jang, Seikwan Oh, Seung-Yeol Nah, Ik-Hyun Cho
Gintonin is a ginseng-derived lysophosphatidic acid receptor (LPAR) ligand. Although previous in vitro and in vivo studies demonstrated the therapeutic role of gintonin against Alzheimer's disease, the neuroprotective effects of gintonin in Parkinson's disease (PD) are still unknown. We investigated whether gintonin (50 and 100 mg/kg/day, p.o., daily for 12 days) had neuroprotective activities against neurotoxicity in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Pre-administration of 100 mg/kg gintonin displayed significantly ameliorating effects in neurological disorders (motor and welfare) as measuring using pole, rotarod, and nest building tests, and in the survival rate...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29874584/the-nad-precursor-nicotinamide-riboside-rescues-mitochondrial-defects-and-neuronal-loss-in-ipsc-and-fly-models-of-parkinson-s-disease
#20
David C Schöndorf, Dina Ivanyuk, Pascale Baden, Alvaro Sanchez-Martinez, Silvia De Cicco, Cong Yu, Ivana Giunta, Lukas K Schwarz, Gabriele Di Napoli, Vasiliki Panagiotakopoulou, Sigrun Nestel, Marcus Keatinge, Jan Pruszak, Oliver Bandmann, Bernd Heimrich, Thomas Gasser, Alexander J Whitworth, Michela Deleidi
While mitochondrial dysfunction is emerging as key in Parkinson's disease (PD), a central question remains whether mitochondria are actual disease drivers and whether boosting mitochondrial biogenesis and function ameliorates pathology. We address these questions using patient-derived induced pluripotent stem cells and Drosophila models of GBA-related PD (GBA-PD), the most common PD genetic risk. Patient neurons display stress responses, mitochondrial demise, and changes in NAD+ metabolism. NAD+ precursors have been proposed to ameliorate age-related metabolic decline and disease...
June 5, 2018: Cell Reports
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