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Parkinsons prevention

Tiffany A Thibaudeau, Raymond T Anderson, David M Smith
Protein accumulation and aggregation with a concomitant loss of proteostasis often contribute to neurodegenerative diseases, and the ubiquitin-proteasome system plays a major role in protein degradation and proteostasis. Here, we show that three different proteins from Alzheimer's, Parkinson's, and Huntington's disease that misfold and oligomerize into a shared three-dimensional structure potently impair the proteasome. This study indicates that the shared conformation allows these oligomers to bind and inhibit the proteasome with low nanomolar affinity, impairing ubiquitin-dependent and ubiquitin-independent proteasome function in brain lysates...
March 15, 2018: Nature Communications
Augusta Pisanu, Laura Boi, Giovanna Mulas, Saturnino Spiga, Sandro Fenu, Anna R Carta
Neuroinflammation is a main component of Parkinson's disease (PD) neuropathology, where unremitting reactive microglia and microglia-secreted soluble molecules such as cytokines, contribute to the neurodegenerative process as part of an aberrant immune reaction. Besides, pro-inflammatory cytokines, predominantly TNF-α, play an important neuromodulatory role in the healthy and diseased brain, being involved in neurotransmitter metabolism, synaptic scaling and brain plasticity. Recent preclinical studies have evidenced an exacerbated neuroinflammatory reaction in the striatum of parkinsonian rats that developed dyskinetic responses following L-DOPA administration...
March 14, 2018: Journal of Neural Transmission
Maria Perez Carrion, Francesca Pischedda, Alice Biosa, Isabella Russo, Letizia Straniero, Laura Civiero, Marianna Guida, Christian J Gloeckner, Nicola Ticozzi, Cinzia Tiloca, Claudio Mariani, Gianni Pezzoli, Stefano Duga, Irene Pichler, Lifeng Pan, John E Landers, Elisa Greggio, Michael W Hess, Stefano Goldwurm, Giovanni Piccoli
Mutations in leucine-rich repeat kinase 2 gene ( LRRK2 ) are associated with familial and sporadic Parkinson's disease (PD). LRRK2 is a complex protein that consists of multiple domains, including 13 putative armadillo-type repeats at the N-terminus. In this study, we analyzed the functional and molecular consequences of a novel variant, E193K, identified in an Italian family. E193K substitution does not influence LRRK2 kinase activity. Instead it affects LRRK2 biochemical properties, such as phosphorylation at Ser935 and affinity for 14-3-3ε...
2018: Frontiers in Molecular Neuroscience
Yi-Qi Lin, Sheng-Di Chen
Increasing evidence indicates a strong association between rapid eye movement sleep behavior disorder (RBD) and Parkinson's disease - cognitive impairment (PD-CI). Numerous longitudinal and cross-sectional studies have shown that RBD may be an important risk factor and predictor of Parkinson's disease - mild cognitive impairment (PD-MCI) and Parkinson's disease dementia (PDD); which may be explained by the association of mechanisms between RBD and PD-CI, including neurotransmitter alterations, genetic mutation, neuroinflammation, alpha-synuclein inclusion, abnormal cerebral metabolism and cortical activity slowing...
April 2018: Sleep Medicine
Hector R Mendez-Gomez, Jasbir Singh, Craig Meyers, Weijun Chen, Oleg S Gorbatyuk, Nicholas Muzyczka
Phospholipase D2 (PLD2), an enzyme involved in vesicle trafficking and membrane signaling, interacts with α-synuclein, a protein known to contribute in the development of Parkinson disease. We previously reported that PLD2 overexpression in rat substantia nigra pars compacta (SNc) causes a rapid neurodegeneration of dopamine neurons, and that α-synuclein suppresses PLD2-induced nigral degeneration (Gorbatyuk et al., 2010). Here, we report that PLD2 toxicity is due to its lipase activity. Overexpression of a catalytically inactive mutant (K758R) of PLD2 prevents the loss of dopaminergic neurons in the SNc and does not show signs of toxicity after 10 weeks of overexpression...
March 8, 2018: Neuroscience
Graziano Onder, Davide L Vetrano, Alessandra Marengoni, J Simon Bell, Kristina Johnell, Katie Palmer
Chronic diseases are considered to be major determinants of frailty and it could be hypothesized that their treatment may counteract the development of frailty. However, the hypothesis that intensive treatment of chronic diseases might reduce the progression of frailty is poorly supported by existing studies. In contrast, some evidence suggests that intensive treatment of chronic diseases may increase negative health outcomes in frail older adults. In particular, if treatment of symptoms related to chronic diseases (i...
March 8, 2018: European Journal of Internal Medicine
Kenneth Maiese
As a result of the advancing age of the global population and the progressive increase in lifespan, neurodegenerative disorders continue to increase in incidence throughout the world. New strategies for neurodegenerative disorders involve the novel pathways of the mechanistic target of rapamycin (mTOR) and the silent mating-type information regulation 2 homolog 1 ( Saccharomyces cerevisiae ) (SIRT1) that can modulate pathways of apoptosis and autophagy. The pathways of mTOR and SIRT1 are closely integrated...
March 9, 2018: Biochemical Society Transactions
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
J S Barajas, D S Peterson
BACKGROUND: Protective steps are critical for fall prevention and are altered in people with Parkinson's disease (PD). Previous work suggests that perturbation training, in which patients are exposed to repeated slips, may improve protective postural responses. However, these studies typically take the average performance of several postural responses before and after training. To reduce falls in the community, training must improve protective stepping after the first perturbation exposure...
March 8, 2018: Journal of Neurology
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
Sumit Jamwal, Puneet Kumar
Alteration in neurotransmitters signaling in basal ganglia has been consistently shown to significantly contribute to the pathophysiological basis of Parkinson's disease and Huntington's disease. Dopamine is important neurotransmitter which play critical role in coordinated body movements. Alteration in level of brain dopamine and receptor radically contribute to irregular movements, glutamate mediated excitotoxic neuronal death and further leads to imbalance in the levels of other neurotransmitters viz. GABA, adenosine, acetylcholine and endocannabinoids...
March 1, 2018: Current Neuropharmacology
Jing Yu, Ning Xu, Ying Zhao, Jinlu Yu
The anterior choroidal artery (AChA) is a critical artery in brain physiology and function. The AChA is involved in many diseases, including aneurysm, brain infarct, Moyamoya disease (MMD), brain tumor, arteriovenous malformation (AVM), etc. The AChA is vulnerable to damage during the treatment of these diseases and is thus a very important vessel. However, a comprehensive systematic review of the importance of the AChA is currently lacking. In this study, we used the PUBMED database to perform a literature review of the AChA to increase our understanding of its role in neurophysiology...
2018: International Journal of Medical Sciences
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
Adam G Kreutzer, James S Nowick
In the more than a century since its identification, Alzheimer's disease has become the archetype of amyloid diseases. The first glimpses of the chemical basis of Alzheimer's disease began with the identification of "amyloid" plaques in the brain in 1892 and extended to the identification of proteinaceous fibrils with "cross-β" structure in 1968. Further efforts led to the discovery of the β-amyloid peptide, Aβ, as a 40- or 42-amino acid peptide that is responsible for the plaques and fibrils...
March 6, 2018: Accounts of Chemical Research
Chadwick W Christine, Peggy Auinger, Amelia Joslin, Yuora Yelpaala, Ralph Green
BACKGROUND: In moderately advanced Parkinson's disease (PD), low serum vitamin B12 levels are common and are associated with neuropathy and cognitive impairment. However, little is known about B12 in early PD. OBJECTIVE: To determine the prevalence of low vitamin B12 status in early PD and whether it is associated with clinical progression. METHODS: We measured vitamin B12 and other B12 status determinants (methylmalonic acid, homocysteine, and holotranscobalamin) in 680 baseline and 456 follow-up serum samples collected from DATATOP participants with early, untreated PD...
March 6, 2018: Movement Disorders: Official Journal of the Movement Disorder Society
A M Ardi Handojoseno, Ganesh R Naik, Moran Gilat, James M Shine, Tuan N Nguyen, Quynh T Ly, Simon J G Lewis, Hung T Nguyen
Freezing of gait (FOG) is an episodic gait disturbance affecting initiation and continuation of locomotion in many Parkinson's disease (PD) patients, causing falls and a poor quality of life. FOG can be experienced on turning and start hesitation, passing through doorways or crowded areas dual tasking, and in stressful situations. Electroencephalography (EEG) offers an innovative technique that may be able to effectively foresee an impending FOG. From data of 16 PD patients, using directed transfer function (DTF) and independent component analysis (ICA) as data pre-processing, and an optimal Bayesian neural network as a predictor of a transition of 5 seconds before the impending FOG occurs in 11 in-group PD patients, we achieved sensitivity and specificity of 85...
2018: Studies in Health Technology and Informatics
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
Ding-Qi Wang, Peng Fu, Chengye Yao, Ling-Shuang Zhu, Tong-Yao Hou, Jian-Guo Chen, Youming Lu, Dan Liu, Ling-Qiang Zhu
Long non-coding RNA (lncRNA) is a kind of non-coding RNA (ncRNA), with a length of 200 nt to 100 kb, that lacks a significant open reading frame (ORF) encoding a protein. lncRNAs are widely implicated in various physiological and pathological processes, such as epigenetic regulation, cell cycle regulation, cell differentiation regulation, cancer, and neurodegenerative diseases, through their interactions with chromatin, protein, and other RNAs. Numerous studies have suggested that lncRNAs are closely linked with the occurrence and development of a variety of diseases, especially neurodegenerative diseases, of which the etiologies are complicated and the underlying mechanisms remain elusive...
March 2, 2018: Molecular Therapy. Nucleic Acids
Etheresia Pretorius, Martin J Page, Sthembile Mbotwe, Douglas B Kell
The thrombin-induced polymerisation of fibrinogen to form fibrin is well established as a late stage of blood clotting. It is known that Parkinson's Disease (PD) is accompanied by dysregulation in blood clotting, but it is less widely known as a coagulopathy. In recent work, we showed that the presence of tiny amounts of bacterial lipopolysaccharide (LPS) in healthy individuals could cause clots to adopt an amyloid form, and this could be observed via scanning electron microscopy (SEM) or via the fluorescence of thioflavin-T...
2018: PloS One
Nicoletta Rizzi, Electra Brunialti, Silvia Cerri, Greta Cermisoni, Giovanna Levandis, Nicoletta Cesari, Adriana Maggi, Fabio Blandini, Paolo Ciana
The Parkinson's disease (PD) evolves over an extended period of time with the onset occurring long before clinical signs begin to manifest. Characterization of the molecular events underlying the PD onset is instrumental for the development of diagnostic markers and preventive treatments, progress in this field is hindered by technical limitations. We applied an imaging approach to demonstrate the activation of Nrf2 transcription factor as a hallmark of neurodegeneration in neurotoxin-driven models of PD. In dopaminergic SK-N-BE neuroblastoma cells, Nrf2 activation was detected in cells committed to die as proven by time lapse microscopy; in the substantia nigra pars compacta area of the mouse brain, the Nrf2 activation preceded dopaminergic neurodegeneration as demonstrated by in vivo and ex vivo optical imaging, a finding confirmed by co-localization experiments carried out by immunohistochemistry...
February 24, 2018: Neurobiology of Disease
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