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NADPH oxidases in Parkinson's disease: a systematic review.

ABSTRACT: 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. Furthermore, knockout or genetic inactivation of NADPH oxidases exert a neuroprotective effect and reduce detrimental aspects of pathology in experimental models of the disease. However, the connections between NADPH oxidases and the biological processes believed to contribute to neuronal death are not well known. This review provides a comprehensive summary of our current understanding about expression and physiological function of NADPH oxidases in neurons, microglia and astrocytes and their pathophysiological roles in PD. It summarizes the findings supporting the role of both microglial and neuronal NADPH oxidases in cellular disturbances associated with PD such as neuroinflammation, alpha-synuclein accumulation, mitochondrial and synaptic dysfunction or disruption of the autophagy-lysosome system. Furthermore, this review highlights different steps that are essential for NADPH oxidases enzymatic activity and pinpoints major obstacles to overcome for the development of effective NADPH oxidases inhibitors for PD.

SUBMITTER: Belarbi K

PROVIDER: S-EPMC5683583 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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NADPH oxidases in Parkinson's disease: a systematic review.

Belarbi Karim K Cuvelier Elodie E Destée Alain A Gressier Bernard B Chartier-Harlin Marie-Christine MC

Molecular neurodegeneration 20171113 1

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 im ...[more]

PMID: 29132391

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Project description:BackgroundParkinson's disease (PD) is a neurodegenerative disorder associated with inferior clinical outcomes after surgical management of many orthopedic conditions. The purpose of this systematic review was to define the clinical, functional, and patient-reported outcomes of shoulder arthroplasty (SA) in patients with PD.MethodsFollowing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic search was completed using the Ovid platform for searches in MEDLINE, EMBASE, Cochrane Central, and Cochrane Systematic Reviews, with additional searches in Web of Science and Scopus. Included studies were full-length, English-language, clinical investigations reporting on SA in patients with PD with at least one clinical outcome.ResultsSeven studies including 7126 patients (7134 SA) met inclusion criteria with a mean age of 72.6 (range, 69.5-75.8 years), 58.9% female, and the average follow-up duration was 65 months (range, 17-119 months). Anatomic total shoulder arthroplasty (aTSA) was the most reported implant surgery (n = 3455, 48.4%) followed by hemiarthroplasty (HA) (n = 2840, 39.8%), and reverse shoulder arthroplasty (RSA) (n = 839,1.8%). SA consistently improved pain. Forward elevation, abduction, and external rotation had a pooled mean increase of 36°, 20°, and 6°, respectively. Complications occurred at a pooled rate of 22.5%, with stiffness (7.1%), need for revision (5.3%), and instability (4.7%) as the most common complications reported. Reoperations inclusive of revisions occurred at a lower pooled rate of 5.6%, with aTSA (n = 201; 9.0%) having the highest rate, followed by HA (n = 158; 7.1%), and then RSA (n = 42; 1.9%).ConclusionsThe results of the present systematic review demonstrate that SA in patients with PD results in consistent pain relief. However, inferior improvements in clinical outcomes may be expected when compared with patients without PD, likely due to the neurodegenerative manifestations of this disorder. In addition, RSA had a lower reoperation rate than HA and aTSA in patients with PD.

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NADPH oxidases in Parkinson's disease: a systematic review.

Publications

NADPH oxidases in Parkinson's disease: a systematic review.

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