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Stress model for neurodegenerative disorders

Alice Biosa, Alvaro Sanchez-Martinez, Roberta Filograna, Ana Terriente-Felix, Sarah M Alam, Mariano Beltramini, Luigi Bubacco, Marco Bisaglia, Alexander J Whitworth
Reactive oxygen species exert important functions in regulating several cellular signalling pathways. However, an excessive accumulation of reactive oxygen species can perturb the redox homeostasis leading to oxidative stress, a condition which has been associated to many neurodegenerative disorders. Accordingly, alterations in the redox state of cells and mitochondrial homeostasis are established hallmarks in both familial and sporadic Parkinson's disease cases. PINK1 and parkin are two genes which account for a large fraction of autosomal recessive early-onset forms of Parkinson's disease and are now firmly associated to both mitochondria and redox homeostasis...
February 24, 2018: Human Molecular Genetics
Alex Yen-Yu Chen, Tim Tully
Parkinson's disease (PD) is a progressive motor neurodegenerative disorder, characterized by a selective loss of dopaminergic neurons in the substantia nigra. The complexity of disease etiology includes both genetic and environmental factors. No effective drug that can modify disease progression and protect dopamine neurons from degeneration is presently available. Human α-Synuclein A30P (A30P) is a mutant gene identified in early onset PD and showed to result selective dopamine neuron loss in transgenic A30P flies and mice...
March 7, 2018: Neurobiology of Disease
Mohammad Javad Ebrahimi, Abbas Aliaghaei, Mahdi Eskandarian Boroujeni, Fariba Khodagholi, Gholamhoussein Meftahi, Mohammad Amin Abdollahifar, Houssein Ahmadi, Samira Danyali, Mahtab Daftari, Yousef Sadeghi
Huntington disease (HD) is an inherited disorder hallmarked by progressive deterioration of specific neurons, followed by movement and cognitive anomalies. Cell therapy approaches in neurodegenerative conditions have concentrated on the replenishment of lost/dying neurons with functional ones. Multipotent mesenchymal stem cells (MSCs) have been represented as a potential remedy for HD. In this study, we evaluated the in vitro and in vivo efficacy of umbilical cord matrix stem cells (UCMSCs) and their paracrine effect against oxidative stress with a specific focus on HD...
March 8, 2018: Neurotoxicity Research
Emily R Seminary, Samantha L Sison, Allison D Ebert
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder caused by the selective loss of the upper and lower motor neurons. Only 10% of all cases are caused by a mutation in one of the two dozen different identified genes, while the remaining 90% are likely caused by a combination of as yet unidentified genetic and environmental factors. Mutations in C9orf72, SOD1 , or TDP-43 are the most common causes of familial ALS, together responsible for at least 60% of these cases. Remarkably, despite the large degree of heterogeneity, all cases of ALS have protein aggregates in the brain and spinal cord that are immunopositive for SOD1, TDP-43, OPTN, and/or p62...
2018: Frontiers in Neuroscience
Fu-Yu Lin, Yi-Chien Yang, Cheng-Li Lin, Lukas Jyuhn-Hsiarn Lee
BACKGROUND: Idiopathic Parkinson's disease (IPD) is a progressive neurodegenerative disorder characterized by typical motor impairment. However, lower urinary tract symptoms, including urinary urgency or frequency, which are non-motor phenomena, occur frequently among patients with IPD. In this study, we assess the risk of overactive bladder (OAB) in patients with IPD. METHODS: The National Health Insurance Research Database of Taiwan was used to identify patients with IPD (IPD cohort) and four-fold controls (non-IPD cohort) from 2000 to 2010...
2018: PloS One
Ai-Min Bao, Dick F Swaab
The quality of postmortem research depends strongly on a thorough clinical investigation and documentation of the patient's disorder and therapies. In addition, a systematic and professional neuropathologic investigation of both cases and controls is absolutely crucial. In the experience of the Netherlands Brain Bank (NBB), about 20% of clinical neurologic diagnoses, despite being made in first-rate clinics, have to be revised or require an extra diagnosis after a complete and thorough review by the NBB. The neuropathology examination may reveal for instance that the "controls" already have preclinical neurodegenerative alterations...
2018: Handbook of Clinical Neurology
Valencia Fernandes, Dilip Sharma, Kiran Kalia, Vinod Tiwari
Astrogliosis is a key contributor for many neurological disorders involving apoptosis, neuroinflammation and subsequent neuronal death. Silibinin, a polyphenol isolated from milk thistle (Silybum marianum), has been shown to suppress the astrocyte activation in various neurodegenerative disorders and also exhibit a neuroprotective role in neuroinflammation-driven oxidative damage. In the present study, we found that treatment with silibinin significantly attenuates LPS- oxidative-nitrosative stress in C6 astrocytoma cells...
February 21, 2018: International Journal of Neuroscience
Asma Zaidi, Mercy Adewale, Lauren McLean, Paul Ramlow
The plasma membrane Ca 2+ -ATPase (PMCA) pumps play a critical role in the maintenance of calcium (Ca 2+ ) homeostasis, crucial for optimal neuronal function and cell survival. Loss of Ca 2+ homeostasis is a key precursor in neuronal dysfunction associated with brain aging and in the pathogenesis of neurodegenerative disorders. In this article, we review evidence showing age-related changes in the PMCAs in synaptic plasma membranes (SPMs) and lipid raft microdomains isolated from rat brain. Both PMCA activity and protein levels decline progressively with increasing age...
January 10, 2018: Neuroscience Letters
Alessandro Tozzi, Michela Tantucci, Saverio Marchi, Petra Mazzocchetti, Michele Morari, Paolo Pinton, Andrea Mancini, Paolo Calabresi
Parkinson's disease (PD) is a neurodegenerative disorder in which genetic and environmental factors synergistically lead to loss of midbrain dopamine (DA) neurons. Mutation of leucine-rich repeated kinase2 (Lrrk2) genes is responsible for the majority of inherited familial cases of PD and can also be found in sporadic cases. The pathophysiological role of this kinase has to be fully understood yet. Hyperactivation of Lrrk2 kinase domain might represent a predisposing factor for both enhanced striatal glutamatergic release and mitochondrial vulnerability to environmental factors that are observed in PD...
February 12, 2018: Cell Death & Disease
Eric N Anderson, Lauren Gochenaur, Aditi Singh, Rogan Grant, Krishani Patel, Simon Watkins, Jane Y Wu, Udai Bhan Pandey
Traumatic brain injury (TBI) has been predicted to be a predisposing factor for Amyotrophic lateral sclerosis (ALS) and other neurological disorders. Despite the importance of TBI in ALS progression, the underlying cellular and molecular mechanisms are still an enigma. Here, we examined the contribution of TBI as an extrinsic factor and investigated if TBI influences the susceptibility of developing neurodegenerative symptoms. To evaluate the effects of TBI in vivo, we applied mild to severe trauma to Drosophila and found that TBI leads to the induction of stress granules (SGs) in the brain...
February 8, 2018: Human Molecular Genetics
Archana S Gurjar, Mrunali N Darekar, Keng Yoon Yeong, Luyi Ooi
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with multiple factors associated with its pathogenesis. Our strategy against AD involves design of multi-targeted 2-substituted-4,5-diphenyl-1H-imidazole analogues which can interact and inhibit AChE, thereby, increasing the synaptic availability of ACh, inhibit BuChE, relieve induced oxidative stress and confer a neuroprotective role. Molecular docking was employed to study interactions within the AChE active site. In silico ADME study was performed to estimate pharmacokinetic parameters...
February 2, 2018: Bioorganic & Medicinal Chemistry
Hao Zhang, Ping Wang, Yixue Xue, Libo Liu, Zhen Li, Yunhui Liu
In middle and old age, Alzheimer's disease (AD) is a progressive neurodegenerative disorder of brain. As an increasingly aging population, AD represents a huge burden for the patients' family and the country. However, current therapeutical strategies have shown limited effectiveness. Allicin, which is the main composition of garlic, was reported to prevent the learning and memory impairment of AD mouse model. As the mechanism is not clear, in this study, we used the APP (amyloid precursor protein)/PS1 (presenilin 1) double transgenic mice, which express human mutant APP and PS1, to determine the protective effect of allicin on neurons...
February 2018: Tissue & Cell
Rosanna Avola, Adriana Carol Eleonora Graziano, Giovanna Pannuzzo, Ferdaous Albouchi, Venera Cardile
The purpose of this research was to explore the behavior of aquaporins (AQPs) in an in vitro model of Parkinson's disease that is a recurrent neurodegenerative disorder caused by the gradual, progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Because of postmortem studies have provided evidences for oxidative damage and alteration of water flow and energy metabolism, we carried out an investigation about AQP4 and 9, demonstrated in the brain to maintain water and energy homeostasis...
February 8, 2018: Molecular and Cellular Neurosciences
Mostafa A Rabie, Mai A Abd El Fattah, Noha N Nassar, Hanan S El-Abhar, Dalaal M Abdallah
MAS receptor (MASR), expressed in several brain areas, conferred neuroprotection against neurodegenerative disorders when activated by angiotensin (Ang) 1-7; however, its role in Parkinson's disease (PD) remains elusive. Intra-striatal post-administration of Ang1-7, using a 6-hydroxydopamine (OHDA) PD model, improved motor performance and muscle coordination. On the molecular level, Ang1-7 upregulated the striatal expression of MASR and caused upsurge in its downstream targets (p-PI3K/p-Akt/p-CREB/BDNF) to phosphorylate TrKB, which in a positive feedback upregulates MASR...
February 8, 2018: Biochemical Pharmacology
Ali Roohbakhsh, Ali Shamsizadeh, A Wallace Hayes, Russel J Reiter, Gholamreza Karimi
Melatonin has long been known for its apparent effects on sleep and circadian rhythm. It may participate as a possible therapeutic agent in neurodegenerative, cardiovascular, and endocrine disorders as well. Autophagy is a lysosomal degradation process that occurs in response to starvation and other stresses. Recent studies have reported that melatonin may modulate the autophagy process. We reviewed the current literature that has reported on how different diseases and/or experimental models change autophagy parameters...
February 3, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Christian Hölscher
Type 2 diabetes is a risk factor for several chronic neurodegenerative disorders such as Alzheimer's or Parkinson's disease. The link appears to be insulin de-sensitisation in the brain. Insulin is an important neuroprotective growth factor. GLP-1 and GIP are growth factors that re-sensitise insulin and GLP-1 mimetics are used in the clinic to treat diabetes. GLP-1 and GIP mimetics initially designed to treat diabetes show good protective effects in animal models of Alzheimer's and Parkinson's disease. Based on these results, several clinical trials have shown first encouraging effects in patients with Alzheimer's or Parkinson' disease...
January 31, 2018: Neuropharmacology
Roberta Balestrino, Anthony H V Schapira
Parkinson disease (PD) is a complex neurodegenerative disease characterised by multiple motor and non-motor symptoms. In the last 20 years, more than 20 genes have been identified as causes of parkinsonism. Following the observation of higher risk of PD in patients affected by Gaucher disease, a lysosomal disorder caused by mutations in the glucocerebrosidase (GBA) gene, it was discovered that mutations in this gene constitute the single largest risk factor for development of idiopathic PD. Patients with PD and GBA mutations are clinically indistinguishable from patients with idiopathic PD, although some characteristics emerge depending on the specific mutation, such as slightly earlier onset...
February 1, 2018: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
Rui Wang, Xiaoyue Han, Jin-Mao You, Fabiao Yu, Lingxin Chen
As new biomarkers, monoamine oxidases (MAOs) play important roles in maintaining the homeostasis of biogenic amines via catalyzing the oxidation of biogenic amines to corresponding aldehydes with the generation of reactive oxygen species (ROS). MAOs have two isoforms, MAO-A and MAO-B. MAO-A is considered to be a major factor of neuropsychiatric and depressive disorders. However, MAO-B is thought to be involved in several neurodegenerative diseases. Therefore, to explore their distinct roles in different diseases, the selective detection of MAOs is essential...
February 5, 2018: Analytical Chemistry
Ahmad Abdullah, Palaniyandi Ravanan
The Endoplasmic Reticulum (ER) plays a fundamental role in executing multiple cellular processes required for normal cellular function. Accumulation of misfolded/unfolded proteins in the ER triggers ER stress which contributes to progression of multiple diseases including neurodegenerative disorders. Recent reports have shown that ER stress inhibition could provide positive response against neuronal injury, ischemia and obesity in in vivo models. Our search towards finding an ER stress inhibitor has led to the functional discovery of kaempferol, a phytoestrogen possessing ER stress inhibitory activity in cultured mammalian cells...
February 1, 2018: Scientific Reports
Vanessa Kappel da Silva, Betânia Souza de Freitas, Victória Campos Dornelles, Luiza Wilges Kist, Maurício Reis Bogo, Milena Carvalho Silva, Emílio Luiz Streck, Jaime Eduardo Hallak, Antônio Waldo Zuardi, José Alexandre S Crippa, Nadja Schröder
Evidence has demonstrated iron accumulation in specific brain regions of patients suffering from neurodegenerative disorders, and this metal has been recognized as a contributing factor for neurodegeneration. Using an experimental model of brain iron accumulation, we have shown that iron induces severe memory deficits that are accompanied by oxidative stress, increased apoptotic markers, and decreased synaptophysin in the hippocampus of rats. The present study aims to characterize iron loading effects as well as to determine the molecular targets of cannabidiol (CBD), the main non-psychomimetic compound of Cannabis sativa, on mitochondria...
January 25, 2018: Brain Research Bulletin
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