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Parkinson's disease and neuroprotection

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https://www.readbyqxmd.com/read/29138117/melatonin-protects-against-behavioral-deficits-dopamine-loss-and-oxidative-stress-in-homocysteine-model-of-parkinson-s-disease
#1
Rajib Paul, Banashree Chetia Phukan, Arokiasamy Justin Thenmozhi, Thamilarasan Manivasagam, Pallab Bhattacharya, Anupom Borah
AIM: Hyperhomocysteinemia and homocysteine (Hcy) mediated dopaminergic neurotoxicity is a matter of concern in the pathophysiology of Parkinson's disease (PD). Our previous study established the involvement of oxidative stress in the substantia nigra (SN) of Hcy rat model of PD; however, the role of antioxidants, such as melatonin, was not tested in this model. MAIN METHODS: Melatonin (10, 20 and 30mg/kg, i.p.) was administered to rats injected with Hcy in right SN (1...
November 11, 2017: Life Sciences
https://www.readbyqxmd.com/read/29137141/steroid-and-xenobiotic-receptor-signalling-in-apoptosis-and-autophagy-of-the-nervous-system
#2
REVIEW
Agnieszka Wnuk, Małgorzata Kajta
Apoptosis and autophagy are involved in neural development and in the response of the nervous system to a variety of insults. Apoptosis is responsible for cell elimination, whereas autophagy can eliminate the cells or keep them alive, even in conditions lacking trophic factors. Therefore, both processes may function synergistically or antagonistically. Steroid and xenobiotic receptors are regulators of apoptosis and autophagy; however, their actions in various pathologies are complex. In general, the estrogen (ER), progesterone (PR), and mineralocorticoid (MR) receptors mediate anti-apoptotic signalling, whereas the androgen (AR) and glucocorticoid (GR) receptors participate in pro-apoptotic pathways...
November 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29137045/the-significance-of-uric-acid-in-the-diagnosis-and-treatment-of-parkinson-disease-an-updated-systemic-review
#3
Zhange Yu, Shuai Zhang, Dongdong Wang, Meng Fan, Fuqiang Gao, Wei Sun, Zirong Li, Shiliang Li
BACKGROUND: Parkinson disease (PD) is a neurodegenerative disease characterized by chronic and progressive loss of dopaminergic neurons in substansia nigra pars compacta. Oxidative stress is proposed to play a critical role in the pathogenesis of PD. Uric acid (UA), as an important physiological antioxidant, is identified a molecular predictor associated with a decreased risk and a slower disease progression for PD and potential neuroprotectant of PD by increasing epidemiological and clinical evidences...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29132545/nanoformulation-a-useful-therapeutic-strategy-for-improving-neuroprotection-and-the-neurorestorative-potential-in-experimental-models-of-parkinson-s-disease
#4
Jose V Lafuente, Catalina Requejo, Alejandro Carrasco, Harkaitz Bengoetxea
Parkinson's disease (PD) is the second most frequent neurodegenerative disorder, but current therapies are only symptomatic. Experimental models are necessary to go deeper in the comprehension of pathophysiological mechanism and to assess new therapeutic strategies. The unilateral 6-hydroxydopamine (6-OHDA) lesion either in medial forebrain bundle (MFB) or into the striatum in rats affords to study various stages of PD depending on the evolution time lapsed. A promising alternative to address the neurodegenerative process is the use of neurotrophic factors; but its clinical use has been limited due to its short half-life and rapid degradation after in vivo administration, along with difficulties for crossing the blood-brain barrier (BBB)...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/29132391/nadph-oxidases-in-parkinson-s-disease-a-systematic-review
#5
REVIEW
Karim Belarbi, Elodie Cuvelier, Alain Destée, Bernard Gressier, Marie-Christine Chartier-Harlin
Parkinson's disease (PD) is a progressive movement neurodegenerative disease associated with a loss of dopaminergic neurons in the substantia nigra of the brain. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, is thought to play an important role in dopaminergic neurotoxicity. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are multi-subunit enzymatic complexes that generate reactive oxygen species as their primary function. Increased immunoreactivities for the NADPH oxidases catalytic subunits Nox1, Nox2 and Nox4 have been reported in the brain of PD patients...
November 13, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29131336/molecular-function-of-%C3%AE-7-nicotinic-receptors-as-drug-targets
#6
Cecilia Bouzat, Matías Lasala, Beatriz Elizabeth Nielsen, Jeremías Corradi, María Del Carmen Esandi
Nicotinic acetylcholine receptors (nAChR) are pentameric ligand-gated ion channels involved in many physiological and pathological processes. In vertebrates, there are seventeen different nAChR subunits that combine to yield a variety of receptors with different pharmacology, function, and localization. The homomeric α7 receptor is one of the most abundant nAChRs in the nervous system and it is also present in non-neuronal cells. It plays important roles in cognition, memory, pain, neuroprotection, and inflammation...
November 13, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29128798/mechanistic-evaluation-of-neuroprotective-effect-of-estradiol-on-rotenone-and-6-ohda-induced-parkinson-s-disease
#7
Dongfang Shen, Xiaoyan Tian, Binbin Zhang, Rongrong Song
BACKGROUND: The present study was intended to investigate the protective effect of estradiol against Parkinson's disease through the use of rotenone-induced neurotoxicity model. METHODS: To define the effect on the behavioral function, Tail suspension test, morris water maize test and cylinder tests were performed. Several biochemical and histological markers related to Parkinson's disease was determined in animal and cell culture models. To evaluate the effect of estradiol on the cellular architecture in rotenone-induced brain tissue, the histopathological examination was carried out by using Haemotoxylin and Eosin staining...
July 8, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29115830/gastrodin-and-isorhynchophylline-synergistically-inhibit-mpp-induced-oxidative-stress-in-sh-sy5y-cells-by-targeting-erk1-2-and-gsk-3%C3%AE-pathways-involvement-of-nrf2-nuclear-translocation
#8
Qiang Li, Chengu Niu, Xiaojie Zhang, Miaoxian Dong
Recently, the pathogenesis of Parkinson's disease (PD) is multifactorial event. Combination therapies might be more effective in controlling the disease. Thus, the studies reported were designed to test the hypothesis that gastrodin (GAS)-induced de novo synthesis of nuclear factor E2-related factor 2 (Nrf2) and isorhynchophylline (IRN) inhibition of Nrf2 nuclear export contribute to their additive or synergistic neuroprotective effect. Here, we have demonstrated that the combination of GAS and IRN (GAS/IRN) protect SH-SY5Y cells against 1-methyl-4-phenylpyridinium (MPP+) toxicity in a synergistic manner...
November 8, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29113464/a-new-treatment-strategy-for-parkinson-s-disease-through-the-gut-brain-axis-the-glucagon-like-peptide-1-receptor-pathway
#9
Dong Seok Kim, Ho-Il Choi, Yun Wang, Yu Luo, Barry J Hoffer, Nigel H Greig
Molecular communications in the gut-brain axis, between the central nervous system and the gastrointestinal tract, are critical for maintaining healthy brain function, particularly in aging. Epidemiological analyses indicate type 2 diabetes mellitus (T2DM) is a risk factor for neurodegenerative disorders including Alzheimer's disease (AD) and Parkinson's diseases (PD) for which aging shows a major correlative association. Common pathophysiological features exist between T2DM, AD, and PD, including oxidative stress, inflammation, insulin resistance, abnormal protein processing, and cognitive decline, and suggest that effective drugs for T2DM that positively impact the gut-brain axis could provide an effective treatment option for neurodegenerative diseases...
September 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29108286/park14-pla2g6-mutants-are-defective-in-preventing-rotenone-induced-mitochondrial-dysfunction-ros-generation-and-activation-of-mitochondrial-apoptotic-pathway
#10
Ching-Chi Chiu, Tu-Hsueh Yeh, Chin-Song Lu, Yin-Cheng Huang, Yi-Chuan Cheng, Ying-Zu Huang, Yi-Hsin Weng, Yu-Chuan Liu, Szu-Chia Lai, Ying-Ling Chen, Yu-Jie Chen, Chao-Lang Chen, Hsin-Yi Chen, Yan-Wei Lin, Hung-Li Wang
Mutations in the gene encoding Ca(2+)-independent phospholipase A2 group 6 (PLA2G6) cause the recessive familial type 14 of Parkinson's disease (PARK14). Mitochondrial dysfunction is involved in the pathogenesis of Parkinson's disease (PD). PLA2G6 is believed to be required for maintaining mitochondrial function. In the present study, rotenone-induced cellular model of PD was used to investigate possible molecular pathogenic mechanism of PARK14 mutant PLA2G6-induced PD. Overexpression of wild-type (WT) PLA2G6 ameliorated rotenone-induced apoptotic death of SH-SY5Y dopaminergic cells...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107085/hsp70-participates-in-pink1-mediated-mitophagy-by-regulating-the-stability-of-pink1
#11
Qian Zheng, Chuxin Huang, Jifeng Guo, Jieqiong Tan, Chunyu Wang, Beisha Tang, Hainan Zhang
INTRODUCTION: Loss-of function mutations in PTEN-induced putative kinase 1 (PINK1) is one of the most common causes of autosomal recessive Parkinson's disease (PD). PINK1-mediated mitophagy is critical to mitochondrial quality control and plays an important role in PD pathogenesis. Therefore, identifying the regulatory mechanisms of PINK1 expression may provide novel opportunities for PD therapy. Heat-shock protein 70kDa (Hsp70) is involved in neuroprotection as a molecular chaperone in neurodegenerative disorders such as PD...
October 28, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29107062/the-anti-aging-protein-klotho-alleviates-injury-of-nigrostriatal-dopaminergic-pathway-in-6-hydroxydopamine-rat-model-of-parkinson-s-disease-involvement-of-pka-camkii-creb-signaling
#12
Tourandokht Baluchnejadmojarad, Seyed-Mohammad Eftekhari, Nida Jamali-Raeufy, Sobhan Haghani, Hossein Zeinali, Mehrdad Roghani
Parkinson's disease (PD) is a prevalent movement disorder in the elderly. PD is hallmarked with progressive deterioration of mesencephalic dopaminergic neurons and development of debilitating motor and non-motor clinical symptoms. Klotho protein is the product of an aging-suppressor gene that its overexpression could protect neurons against oxidative injury. This study was undertaken to explore whether exogenous klotho could alleviate injury of nigrostriatal dopaminergic pathway in 6-hydroxydopamine (6-OHDA) rat model of PD...
October 31, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29101940/rem-sleep-behavior-disorder-diagnosis-clinical-implications-and-future-directions
#13
REVIEW
Erik K St Louis, Bradley F Boeve
Rapid eye movement sleep behavior disorder (RBD) is diagnosed by a clinical history of dream enactment accompanied by polysomnographic rapid eye movement sleep atonia loss (rapid eye movement sleep without atonia). Rapid eye movement sleep behavior disorder is strongly associated with neurodegenerative disease, especially synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. A history of RBD may begin several years to decades before onset of any clear daytime symptoms of motor, cognitive, or autonomic impairments, suggesting that RBD is the presenting manifestation of a neurodegenerative process...
November 2017: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/29100803/the-effects-of-cysteamine-in-a-mouse-model-of-levodopa-induced-dyskinesias
#14
Linda S David, Martine Saint-Pierre, Jérôme Lamontagne-Proulx, Francesca Cicchetti
Levo-dopa (L-DOPA) has shown significant and long-lasting efficacy in the treatment of motor features characteristic of Parkinson's disease (PD). However, the effects tend to wear off at a time typically when side-effects, such as L-DOPA induced dyskinesias (LIDs), start to emerge and for which the treatment options are very limited. In recent years, we have reported on the neuroprotective and neurorestorative properties of the compounds cystamine/cysteamine in ameliorating several aspects of PD. Building on these observations, we set out to further evaluate the benefits of cysteamine on LIDs...
October 31, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29100525/modulating-the-catalytic-activity-of-ampk-has-neuroprotective-effects-against-%C3%AE-synuclein-toxicity
#15
Wojciech Bobela, Sameer Nazeeruddin, Graham Knott, Patrick Aebischer, Bernard L Schneider
BACKGROUND: Metabolic perturbations and slower renewal of cellular components associated with aging increase the risk of Parkinson's disease (PD). Declining activity of AMPK, a critical cellular energy sensor, may therefore contribute to neurodegeneration. METHODS: Here, we overexpress various genetic variants of the catalytic AMPKα subunit to determine how AMPK activity affects the survival and function of neurons overexpressing human α-synuclein in vivo. RESULTS: Both AMPKα1 and α2 subunits have neuroprotective effects against human α-synuclein toxicity in nigral dopaminergic neurons...
November 3, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29089984/interleukin-4-induced-neuroprotection-and-regulation-of-microglia-activation-as-a-therapeutic-approach-in-the-mptp-model-of-parkinson-s-disease
#16
Björn Spittau
No abstract text is available yet for this article.
September 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29082547/-11-c-pe2i-and-18-f-dopa-pet-for-assessing-progression-rate-in-parkinson-s-a-longitudinal-study
#17
Weihua Li, Nick P Lao-Kaim, Andreas A Roussakis, Antonio Martín-Bastida, Natalie Valle-Guzman, Gesine Paul, Clare Loane, Håkan Widner, Marios Politis, Tom Foltynie, Roger A Barker, Paola Piccini
BACKGROUND: (18) F-dopa PET measuring aromatic l-amino acid decarboxylase activity is regarded as the gold standard for evaluating dopaminergic function in Parkinson's disease. Radioligands for dopamine transporters are also used in clinical trials and for confirming PD diagnosis. Currently, it is not clear which imaging marker is more reliable for assessing clinical severity and rate of progression. The objective of this study was to directly compare (18) F-dopa with the highly selective dopamine transporter radioligand (11) C-PE2I for the assessment of motor severity and rate of progression in PD...
October 30, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29080525/neuroprotection-through-flavonoid-enhancement-of-the-glyoxalase-pathway
#18
Joel R Frandsen, Prabagaran Narayanasamy
The glyoxalase pathway functions to detoxify reactive dicarbonyl compounds, most importantly methylglyoxal. The glyoxalase pathway is an antioxidant defense mechanism that is essential for neuroprotection. Excessive concentrations of methylglyoxal have deleterious effects on cells, leading to increased levels of inflammation and oxidative stress. Neurodegenerative diseases - including Alzheimer's, Parkinson's, Aging and Autism Spectrum Disorder - are often induced or exacerbated by accumulation of methylglyoxal...
October 18, 2017: Redox Biology
https://www.readbyqxmd.com/read/29079145/nrf2-mediated-neuroprotection-by-manf-against-6-ohda-induced-cell-damage-via-pi3k-akt-gsk3%C3%AE-pathway
#19
Jingxing Zhang, Weifang Tong, Hui Sun, Ming Jiang, Yijue Shen, Yigang Liu, Hua Gu, Jia Guo, Jianmin Fang, Lingjing Jin
Oxidative stress and apoptosis are thought to be broadly involved in the pathogenesis of Parkinson's disease. We previously reported that Mesencephalic astrocyte-derived neurotrophic factor (MANF) possesses anti-oxidation and anti-apoptotic effects against 6-OHDA-induced neurotoxicity, but the specific molecular mechanism remains unclear. In this study, we showed that MANF up-regulates the expression of nuclear factor erythroid 2-related factor (Nrf2) and promotes its translocation into the nucleus. The anti-oxidation and anti-apoptotic effects of MANF could be partially blocked by inhibitor or shRNA-mediated knockdown of Nrf2...
October 25, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/29079063/neuroprotective-and-neuro-restorative-effects-of-minocycline-and-rasagiline-in-a-zebrafish-6-hydroxydopamine-model-of-parkinson-s-disease
#20
Aileen Cronin, Maura Grealy
Parkinson's disease is a common, debilitating, neurodegenerative disorder for which the current gold standard treatment, levodopa (L-DOPA) is symptomatic. There is an urgent, unmet need for neuroprotective or, ideally, neuro-restorative drugs. We describe a 6-hydroxydopamine (6-OHDA) zebrafish model to screen drugs for neuroprotective and neuro-restorative capacity. Zebrafish larvae at two days post fertilization were exposed to 6-OHDA for three days, with co-administration of test drugs for neuroprotection experiments, or for 32 h, with subsequent treatment with test drugs for neuro-restoration experiments...
October 24, 2017: Neuroscience
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