Targeting urate to reduce oxidative stress in Parkinson disease.

Targeting urate to reduce oxidative stress in Parkinson disease. Exp Neurol. 2017 Jun 13;: Authors: Crotty GF, Ascherio A, Schwarzschild MA Abstract Oxidative stress has been implicated as a core contributor to the initiation and progression of multiple neurological diseases. Genetic and environmental factors can produce oxidative stress through mitochondrial dysfunction leading to the degeneration of dopaminergic and other neurons underlying Parkinson disease (PD). Although clinical trials of antioxidants have thus far failed to demonstrate slowed progression of PD, oxidative stress remains a compelling target. Rather than prompting abandonment of antioxidant strategies, these failures have raised the bar for justifying drug and dosing selections and for improving study designs to test for disease modification by antioxidants. Urate, the main antioxidant found in plasma as well as the end product of purine metabolism in humans, has emerged as a promising potential neuroprotectant with advantages that distinguish it from previously tested antioxidant agents. Uniquely, higher urate levels in plasma or cerebrospinal fluid (CSF) have been linked to both a lower risk of developing PD and to a slower rate of its subsequent progression in numerous large prospective epidemiological and clinical cohorts. Laboratory evidence that urate confers neuroprotection in cellular and animal models of PD, possibly via the Nrf2 antioxidant response pathway, further strength...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research

Related Links:

Publication date: Available online 17 October 2019Source: Molecular Aspects of MedicineAuthor(s): J.V. Cabral-Costa, A.J. KowaltowskiAbstractThe brain is highly dependent on mitochondrial energy metabolism. As a result, mitochondrial dysfunction is a central aspect of many adult-onset neurological diseases, including stroke, ALS, Alzheimer's, Huntington's, and Parkinson's diseases. We review here how different mitochondrial functions, including oxidative phosphorylation, mitochondrial dynamics, oxidant generation, cell death regulation, Ca2+ homeostasis, and proteostasis are involved in these disorders.
Source: Molecular Aspects of Medicine - Category: Molecular Biology Source Type: research
Parkinson disease is a complex, age-related, neurodegenerative disease associated with dopamine deficiency and both motor and nonmotor deficits. Many environmental and genetic factors influence Parkinson disease risk, with different factors predominating in different patients. These factors converge on specific pathways, including mitochondrial dysfunction, oxidative stress, protein aggregation, impaired autophagy, and neuroinflammation. Ultimately, treatment of Parkinson disease may focus on targeted therapies for pathophysiologically defined subtypes of Parkinson disease patients.
Source: Clinics in Geriatric Medicine - Category: Geriatrics Authors: Source Type: research
Publication date: Available online 15 October 2019Source: Stem Cell ResearchAuthor(s): Mazid Md Abdul, David P. Ibañez, Ping Zhao, Hao Liu, Xiaofen Zhong, Yingying Li, Meng Zhang, Wenjuan Li, Yunpan Li, Carl Ward, Shuhan Chen, Dongye Wang, Baoming Qin, Miguel A. Esteban, Xiwei Wang, Wenxia Fan, Zhiwei LuoAbstractFamilial Parkinson's disease (PD) can be caused by deleterious mutations in PINK1 (encoding PINK1) in an autosomal recessive manner. Functional studies suggest that PINK1 works as a regulator of mitochondrial homeostasis. However, how loss of PINK1 induces dopaminergic neuron degeneration is still unclear. H...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Publication date: Available online 15 October 2019Source: Stem Cell ResearchAuthor(s): Meng Zhang, David P. Ibañez, Wenxia Fan, Hao Liu, Xiaofen Zhong, Xiwei Wang, Yingying Li, Mazid Md.Abdul, Wenjuan Li, Yunpan Li, Carl Ward, Shuhan Chen, Dongye Wang, Baoming Qin, Miguel A. Esteban, Ping Zhao, Zhiwei LuoAbstractLoss of function mutations in PARK2 (encoding PARKIN) cause autosomal recessive Parkinson's disease (PD), which often manifests at a juvenile age. Molecular and biochemical studies show that PARKIN functions as an E3 ubiquitin ligase controlling mitochondrial homeostasis. Yet, the exact mechanisms are unclea...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Publication date: Available online 14 October 2019Source: Neuroscience LettersAuthor(s): Tanapol Limboonreung, Patoomratana Tuchinda, Sukumal ChongthammakunAbstractChrysoeriol is a plant flavone extracted from the roots and leaves of the genus Phyllanthus. Although many biological properties of chrysoeriol have been reported, such as its antioxidant and anti-inflammatory activities, the effects of chrysoeriol on the cellular models of Parkinson's disease (PD) have not yet been elucidated. In the present study, we aimed to investigate whether chrysoeriol prevents neurotoxicity induced by 1-methyl-4-phenylpyridinium iodide (...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
In conclusion, a polypharmacology approach of combining established, prolongevity drug inhibitors of specific nodes may be the most effective way to target the nutrient-sensing network to improve late-life health. Deletion of p38α in Neurons Slows Neural Stem Cell Decline and Loss of Cognitive Function in Mice https://www.fightaging.org/archives/2019/10/deletion-of-p38%ce%b1-in-neurons-slows-neural-stem-cell-decline-and-loss-of-cognitive-function-in-mice/ Researchers here provide evidence for p38α to be involved in the regulation of diminished neural stem cell activity with age. It is thought...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Publication date: 2019Source: International Review of Neurobiology, Volume 147Author(s): Xiaojiao Xu, Zhenfa Fu, Weidong LeAbstractParkinson's disease (PD) is one of the most common neurodegenerative diseases in the world. Unfortunately, most of the currently used clinical therapies against PD are symptomatic and there is still no remedy can stop disease progression. Collective evidence shows that various kinds of exercise may reduce the risk of PD and do have positive impacts on both motor and nonmotor symptoms of PD. Additionally, exercise can also ameliorate the side effects such as wearing-off and dyskinesia induced by...
Source: International Review of Neurobiology - Category: Neuroscience Source Type: research
Abstract Parkin and alpha-synuclein (α-syn) are two key proteins involved in the pathophysiology of Parkinson's disease (PD). Oligomerization/aggregation and excessive secretion of α-syn contributes to PD through free radical stress, mitochondrial impairment, and synaptic dysfunction. Parkin, an E3 ubiquitin ligase, is considered to be a pleiotropic, neuroprotective protein that modulates metabolic turnover and the accumulation of α-syn. This is in addition to parkin's role in counteracting the more distant effects of α-syn on cellular survival by altering proteasomal, autophagic, and calpa...
Source: Acta Neurobiologiae Experimentalis - Category: Neurology Authors: Tags: Acta Neurobiol Exp (Wars) Source Type: research
Abstract Neurodegeneration entails progressive loss of neuronal structure as well as function leading to cognitive failure, apathy, anxiety, irregular body movements, mood swing and ageing. Proteomic dysregulation is considered the key factor for neurodegeneration. Mechanisms involving deregulated processing of proteins such as amyloid beta (Aβ) oligomerization; tau hyperphosphorylation, prion misfolding; α-synuclein accumulation/lewy body formation, chaperone deregulation, acetylcholine depletion, adenosine 2A (A2A) receptor hyperactivation, secretase deregulation, leucine-rich repeat kinase 2 (LRRK2) ...
Source: Cellular and Molecular Neurobiology - Category: Cytology Authors: Tags: Cell Mol Neurobiol Source Type: research
Abstract Abnormal protein aggregation has been linked to many neurodegenerative diseases, including Parkinson's disease (PD). The main pathological hallmark of PD is the formation of Lewy bodies (LBs) and Lewy neurites, both of which contain the presynaptic protein alpha-synuclein (α-syn). Under normal conditions, native α-syn exists in a soluble unfolded state but undergoes misfolding and aggregation into toxic aggregates under pathological conditions. Toxic α-syn species, especially oligomers, can cause oxidative stress, membrane penetration, synaptic and mitochondrial dysfunction, as well as o...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research
More News: Brain | Clinical Trials | Environmental Health | Epidemiology | Genetics | Laboratory Medicine | Mitochondrial Disease | Neurology | Parkinson's Disease | Study