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Parkinson's disease and neuroprotection

Manon Auffret, Sophie Drapier, Marc Vérin
Apomorphine is now recognized as the oldest antiparkinsonian drug on the market. Though still underused, it is increasingly prescribed in Europe for patients with advanced Parkinson's disease (PD) with motor fluctuations. However, its history is far from being limited to movement disorders. This paper traces the history of apomorphine, from its earliest empirical use, to its synthesis, pharmacological development, and numerous indications in human and veterinary medicine, in light of its most recent uses and newest challenges...
March 15, 2018: Drugs in R&D
Ren-Hong Du, Hong-Bin Sun, Zhao-Li Hu, Ming Lu, Jian-Hua Ding, Gang Hu
Classical activation (M1 phenotype) and alternative activation (M2 phenotype) are the two polars of microglial activation states that can produce either neurotoxic or neuroprotective effects in the immune pathogenesis of Parkinson's disease (PD). Exploiting the beneficial properties of microglia cells by modulating their polarization states provides great potential for the treatment of PD. However, the mechanism that regulates microglia polarization remains elusive. Here we demonstrated that Kir6.1-containing ATP-sensitive potassium (Kir6...
March 14, 2018: Cell Death & Disease
Beth Grimmig, Lauren Daly, Meena Subbarayan, Ched Hudson, Robert Williamson, Kevin Nash, Paula C Bickford
Parkinson's disease (PD) is the second most common neurodegenerative disorder and prevalence increases with age. Normal physiological changes that occur during the aging process reflect the pathological characteristics of Parkinson's disease. It is also recognized that age related changes significantly interact with the pathological mechanisms that underlie the neurodegeneration in PD and perpetuate the disease process. Despite the fact that aging is considered to be a primary risk factor for developing PD, the use of aged animal models are still under-utilized in pre-clinical research, thus reducing the translatability of experimental findings...
February 13, 2018: Oncotarget
Damla Tas, Luca Stickley, Federico Miozzo, Rafael Koch, Nicolas Loncle, Virginie Sabado, Bettina Gnägi, Emi Nagoshi
Forkhead box (FOXO) proteins are evolutionarily conserved, stress-responsive transcription factors (TFs) that can promote or counteract cell death. Mutations in FOXO genes are implicated in numerous pathologies, including age-dependent neurodegenerative disorders, such as Parkinson's disease (PD). However, the complex regulation and downstream mechanisms of FOXOs present a challenge in understanding their roles in the pathogenesis of PD. Here, we investigate the involvement of FOXO in the death of dopaminergic (DA) neurons, the key pathological feature of PD, in Drosophila...
March 12, 2018: PLoS Genetics
Jessica M de Souza, Bruno D C Goncalves, Marcus V Gomez, Luciene B Vieira, Fabiola M Ribeiro
Neurodegenerative diseases affect millions of individuals worldwide. So far, no disease-modifying drug is available to treat patients, making the search for effective drugs an urgent need. Neurodegeneration is triggered by the activation of several cellular processes, including oxidative stress, mitochondrial impairment, neuroinflammation, aging, aggregate formation, glutamatergic excitotoxicity, and apoptosis. Therefore, many research groups aim to identify drugs that may inhibit one or more of these events leading to neuronal cell death...
2018: Frontiers in Pharmacology
Ann Kristin Frøyset, Amanda J Edson, Naouel Gharbi, Essa A Khan, Daniel Dondorp, Qing Bai, Ettore Tiraboschi, Maximiliano L Suster, Joanne B Connolly, Edward A Burton, Kari E Fladmark
DJ-1, a Parkinson's disease-associated protein, is strongly up-regulated in reactive astrocytes in Parkinson's disease. This is proposed to represent a neuronal protective response, although the mechanism has not yet been identified. We have generated a transgenic zebrafish line with increased astroglial DJ-1 expression driven by regulatory elements from the zebrafish GFAP gene. Larvae from this transgenic line are protected from oxidative stress-induced injuries as caused by MPP+ , a mitochondrial complex I inhibitor shown to induce dopaminergic cells death...
February 17, 2018: Redox Biology
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
Cybelle Façanha Barreto Medeiros-Linard, Belmira Lara da Silveira Andrade-da-Costa, Ricielle Lopes Augusto, Adriana Sereniki, Maria Teresa Sales Trevisan, Renata de Cássia Ribas Perreira, Francisco Thiago Correia de Souza, Glauber Ruda Feitoza Braz, Claudia Jacques Lagranha, Ivone Antônia de Souza, Almir Gonçalves Wanderley, Soraya S Smailli, Simone Sette Lopes Lafayette
Anacardic acids (AAs) are alkyl phenols mainly presenting in cashew nuts. The antioxidant effects of these compounds have been an area of interest in recent research, with findings suggesting potential therapeutic use for certain diseases. Nevertheless, none of these studies were performed in order to test the hypothesis of whether anacardic acids are capable of preventing behavioral changes and oxidative stress induced by the pesticide rotenone in experimental model of Parkinson's disease. In our research, adult male rats were treated orally with AAs (1, 3, 10, 25, 50, or 100 mg/kg/day) 1 h before rotenone (3 mg/kg; s...
March 8, 2018: Neurotoxicity Research
Matthew L Neal, Alexa M Boyle, Kevin M Budge, Fayez F Safadi, Jason R Richardson
BACKGROUND: Neuroinflammation is one of the hallmarks of neurodegenerative diseases, such as Parkinson's disease (PD). Activation of glial cells, including microglia and astrocytes, is a characteristic of the inflammatory response. Glycoprotein non-metastatic melanoma protein B (GPNMB) is a transmembrane glycoprotein that releases a soluble signaling peptide when cleaved by ADAM10 or other extracellular proteases. GPNMB has demonstrated a neuroprotective role in animal models of ALS and ischemia...
March 8, 2018: Journal of Neuroinflammation
Mariachiara Zuccarini, Patricia Giuliani, Monica Frinchi, Giuseppa Mudò, Rosa Maria Serio, Natale Belluardo, Silvana Buccella, Marzia Carluccio, Daniele F Condorelli, Francesco Caciagli, Renata Ciccarelli, Patrizia Di Iorio
Mounting evidence suggests that the guanine-based purines stand out as key player in cell metabolism and in several models of neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases. Guanosine (GUO) and guanine (GUA) are extracellular signaling molecules derived from the breakdown of the correspondent nucleotide, GTP, and their intracellular and extracellular levels are regulated by the fine-tuned activity of two major enzymes, purine nucleoside phosphorylase (PNP) and guanine deaminase (GDA)...
2018: Frontiers in Pharmacology
Yingjuan Liu, Lihua Geng, Jingjing Zhang, Jing Wang, Qi Zhang, Delin Duan, Quanbin Zhang
Parkinson's disease (PD) is a neurodegenerative movement disorder that is caused by a selective loss of dopaminergic neurons. Current PD treatments provide symptomatic relief but do not prevent or decelerate disease progression. Previous studies have suggested that acetylated and phosphorylated porphyran, derived from Porphyra , produces a neuroprotective effect against 6-OHDA-induced damage. Due to its antioxidant and neuroprotective potential, this study evaluates whether oligo-porphyran (OP) could be beneficial in an experimental model of PD in mice...
March 6, 2018: Marine Drugs
Liyan Hou, Yuning Che, Fuqiang Sun, Qingshan Wang
Beyond nigrostriatal dopaminergic system, the noradrenergic locus coeruleus (LC/NE) neurons are also degenerated in patients with Parkinson's disease (PD), the second most common neurodegenerative disorder. We previously reported that microglia-mediated neuroinflammation contributes to LC/NE neurodegeneration. The purpose of this study is aimed to test whether taurine, an endogenous amino acid, could be able to protect LC/NE neurons through inhibition of microglial activation using paraquat and maneb-induced mouse PD model...
March 5, 2018: Amino Acids
Luca Bors, Ágnes Bajza, Dorottya Kocsis, Franciska Erdő
Coffee consumption had already been described in the 15th century. The spreading of coffee drinking was not only a consequence of its delicious aromatic taste, but also of its pharmacological effects, especially due to its caffeine content. In this review, the mechanisms behind its complex stimulatory effects and the latest studies on the possible new therapeutic indications of caffeine are summarized. Several papers reported the neuroprotective (in Alzheimer's and Parkinson's disease) and hepatoprotective profiles of caffeine, and we show the most promising new results about its preventive properties in dermal malignancies...
March 2018: Orvosi Hetilap
Esteban Luna, Samantha C Decker, Dawn M Riddle, Anna Caputo, Bin Zhang, Tracy Cole, Carrie Caswell, Sharon X Xie, Virginia M Y Lee, Kelvin C Luk
The accumulation of misfolded α-synuclein (aSyn) and neuron loss define several neurodegenerative disorders including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). However, the precise relationship between pathology and neurotoxicity and why these processes disproportionately affect certain neuron subpopulations are poorly understood. We show here that Math2-expressing neurons in the hippocampal Cornu ammonis (CA), a region significantly affected by aSyn pathology in advanced PD and DLB, are highly susceptible to pathological seeding with pre-formed fibrils (PFFs), in contrast to dentate gyrus neurons, which are relatively spared...
March 3, 2018: Acta Neuropathologica
Sunaina Sharma, Puneet Kumar, Rahul Deshmukh
Parkinson's disease is a leading hypokinetic disorder characterized by selective loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) region of mid-brain. Degeneration of dopaminergic neurons is considered to be due to oxidative stress, neuroinflammation, disturbed calcium homeostasis and glutamate excitotoxicity etc. Spermidine is a polyamine which counteracts age associated cell death by scavenging free radical formation, activates authophagic machinery by enhancing formation of autophagosome, and antagonizes NMDA receptor...
February 28, 2018: Neurochemistry International
Rihua Wang, Xue Zhao, Jin Xu, Yifan Wen, Aiping Li, Ming Lu, Jianwei Zhou
Astrocytic JWA exerts neuroprotective roles by alleviating oxidative stress and inhibiting inflammation. However, the molecular mechanisms of how astrocytic JWA is involved in dopaminergic neurodegeneration in Parkinson's disease (PD) remain largely unknown. In this study, we found that astrocyte-specific JWA knockout mice (JWA CKO) exacerbated dopamine (DA) neuronal loss and motor dysfunction, and reduced the levels of DA and its metabolites in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine/probenecid (MPTP/p)-induced PD model...
March 2, 2018: Cell Death & Disease
Mona Dehhaghi, Fatemeh Mohammadipanah, Gilles J Guillemin
Age-related disorders impose noticeable financial and emotional burdens on society. This impact is becoming more prevalent with the increasing incidence of neurodegenerative diseases and is causing critical concerns for treatment of patients worldwide. Parkinson's disease, Alzheimer's disease, multiple sclerosis and motor neuron disease are the most prevalent and the most expensive to treat neurodegenerative diseases globally. Therefore, exploring effective therapies to overcome these disorders is a necessity...
February 27, 2018: Neurotoxicology
B S Alghamdi
Melatonin is a neurohormone secreted from the pineal gland and has a wide-ranging regulatory and neuroprotective role. It has been reported that melatonin level is disturbed in some neurological conditions such as stroke, Alzheimer's disease, and Parkinson's disease, which indicates its involvement in the pathophysiology of these diseases. Its properties qualify it to be a promising potential therapeutic neuroprotective agent, with no side effects, for some neurological disorders. This review discusses and localizes the effect of melatonin in the pathophysiology of some diseases...
March 1, 2018: Journal of Neuroscience Research
Farida Larit, Khaled M Elokely, Narayan D Chaurasiya, Samira Benyahia, Manal A Nael, Francisco León, Mohammad Sanad Abu-Darwish, Thomas Efferth, Yan-Hong Wang, Djamila Belouahem-Abed, Samir Benayache, Babu L Tekwani, Stephen J Cutler
BACKGROUND: Monoamine oxidases (MAOs) are outer mitochondrial membrane flavoenzymes. They catalyze the oxidative deamination of a variety of neurotransmitters. MAO-A and MAO-B may be considered as targets for inhibitors to treat neurodegenerative diseases and depression and for managing symptoms associated with Parkinson's and Alzheimer's diseases. PURPOSE: The objective was to evaluate the inhibitory effect of Hypericum afrum and Cytisus villosus against MAO-A and B and to isolate the compounds responsible for the MAO-inhibitory activity...
February 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Shu-Qing Chen, Ze-Shi Wang, Yi-Xiao Ma, Wei Zhang, Jian-Liang Lu, Yue-Rong Liang, Xin-Qiang Zheng
As the population ages, neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD) impose a heavy burden on society and families. The pathogeneses of PD and AD are complex. There are no radical cures for the diseases, and existing therapeutic agents for PD and AD have diverse side effects. Tea contains many bioactive components such as polyphenols, theanine, caffeine, and theaflavins. Some investigations of epidemiology have demonstrated that drinking tea can decrease the risk of PD and AD...
February 25, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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