The potential benefits of dental implants on the oral health quality of life of people with Parkinson’s disease

Objective: To investigate how dental implants impact on the oral health quality of life of people with Parkinson’s disease (PD). Background: PD is a progressive neurological disorder that can result in a number of oral health care challenges, including denture difficulties. Lack of evidence related to use of implants in PD prompted this study to investigate their use in this group of people. Materials and methods: Nine people with PD were provided with either fixed or removable prostheses using Astra‐Tech implants. Participants completed the socio‐dental questionnaire, ‘The Dental Impact on Daily Living Assessment’ (DIDL) prior to implant surgery, and at 3 and 12 months after provision of the final prosthesis. DIDL comprises two components – the Oral Health Quality of Life Inventory (OH‐QoL) and the Self‐Reported Assessment of Oral Health and Functional Status (SROH). Results: Nine people (with an age range of 54–77 years) had implants placed. The implant success rate was 85 and 81% in the maxilla and mandible, respectively. The OH‐QoL and SROH results (analysed using the one‐way analysis of variance and pairwise multiple comparisons) demonstrated a significant improvement in the domains of eating and satisfaction with the prosthesis after 3 months, which was maintained at the twelve month review. The OH‐QoL indicated a gradual improvement in oral well‐being over the 12‐month period. Conclusion: The oral health quality of life of people with PD was improved by the use of dental implants, indicating this as a viable treatment option.     

Endometrial stem cell transplantation restores dopamine production in a Parkinson’s disease model

Parkinson’s disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic neurons. Adult human endometrial derived stem cells (HEDSC), a readily obtainable type of mesenchymal stem‐like cell, were used to generate dopaminergic cells and for transplantation. Cells expressing CD90, platelet derived growth factor (PDGF)‐Rβ and CD146 but not CD45 or CD31 were differentiated in vitro into dopaminergic neurons that exhibited axon projections, pyramidal cell bodies and dendritic projections that recapitulate synapse formation; these cells also expressed the neural marker nestin and tyrosine hydroxylase, the rate‐limiting enzyme in dopamine synthesis. Whole cell patch clamp recording identified G‐protein coupled inwardly rectifying potassium current 2 channels characteristic of central neurons. A 1‐methyl 4‐phenyl 1,2,3,6‐tetrahydro pyridine induced animal model of PD was used to demonstrate the ability of labelled HEDSC to engraft, migrate to the site of lesion, differentiate in vivo and significantly increase striatal dopamine and dopamine metabolite concentrations. HEDSC are a highly inducible source of allogenic stem cells that rescue dopamine concentrations in an immunocompetent PD mouse model.     

Nitric oxide synthase regulation and diversity: Implications in Parkinson’s disease

Nitric oxide (NO) is a janus faced chemical messenger, which, in the recent years, has been the focus of neurobiologists for its involvement in neurodegenerative disorders in particular, Parkinson's disease (PD). Nitric oxide synthase, the key enzyme involved in NO production exists in three known isoforms. The neuronal and inducible isoforms have been implicated in the pathogenesis of PD. These enzymes are subject to complex expressional and functional regulation involving mRNA diversity, phosphorylation and protein interaction. In the recent years, mRNA diversity and polymorphisms have been identified in the NOS isoforms. Some of these genetic variations have been associated with PD, indicating an etiological role for the NOS genes. This review mainly focuses on the NOS genes - their differential regulation and genetic heterogeneity, highlighting their significance in the pathobiology of PD.     

Role of post-translational modifications on the alpha-synuclein aggregation-related pathogenesis of Parkinson’s disease

Together with neuronal loss, the existence of insoluble inclusions of alpha-synuclein (α-syn) in the brain is widely accepted as a hallmark of synucleinopathies including Parkinson’s disease (PD), multiple system atrophy, and dementia with Lewy body. Because the α-syn aggregates are deeply involved in the pathogenesis, there have been many attempts to demonstrate the mechanism of the aggregation and its potential causative factors including post-translational modifications (PTMs). Although no concrete conclusions have been made based on the previous study results, growing evidence suggests that modifications such as phosphorylation and ubiquitination can alter α-syn characteristics to have certain effects on the aggregation process in PD; either facilitating or inhibiting fibrillization. In the present work, we reviewed studies showing the significant impacts of PTMs on α-syn aggregation. Furthermore, the PTMs modulating α-syn aggregation-induced cell death have been discussed.      

Kynurenines,neurodegeneration and Alzheimer’s disease

Alzheimer’s disease (AD) is one of the major causes of dementia. The pathogenesis of the disease is not entirely understood, but the amyloid β peptide (Aβ) and the formation of senile plaques seem to play pivotal roles. Oligomerization of the Aβ is thought to trigger a cascade of events, including oxidative stress, glutamate excitotoxicity and inflammation. The kynurenine (KYN) pathway is the major route for the metabolism of the essential amino acid tryptophan. Some of the metabolites of this pathway, such as 3-hydroxykynurenine and quinolinic acid, are known to have neurotoxic properties, whereas others, such as kynurenic acid, are putative neuroprotectants. Among other routes, the KYN pathway has been shown to be involved in AD pathogenesis, and connections to other known mechanisms have also been demonstrated. Oxidative stress, glutamate excitotoxicity and the neuroinflammation involved in AD pathogenesis have been revealed to be connected to the KYN pathway. Intervention at these key steps may serve as the aim of potential therapy.     

On the reconceptualization of Alzheimer’s disease

In the hope of future treatments to prevent or slow down the disease, there is a strong movement towards an ever‐earlier detection of Alzheimer’s disease (AD). In conjunction with scientific developments, this has prompted a reconceptualization of AD, as a slowly progressive pathological process with a long asymptomatic phase. New concepts such as ‘preclinical’ and ‘prodromal’ AD have been introduced, raising a number of conceptual and ethical questions. We evaluate whether these new concepts are theoretically defensible, in light of theories of health and disease, and whether they should be understood as disease or as an at‐risk state. We introduce a pragmatic view on disease concepts and argue that an evaluation of the reconceptualization of AD should also take its aims and effects into account, and assess their ethical acceptability. The reconceptualization of AD is useful to coordinate research into preventive strategies, and may potentially benefit future patients. However, in the short term, early detection and labelling of ‘preclinical AD’ can potentially harm people. Since there is no treatment available and the predictive value is unclear, it may only create a group of ‘patients‐in‐waiting’ who may suffer from anxiety, uncertainty and stigmatization, but will never actually develop dementia. We conclude that only if the promise of preventive medication materializes, will the reconceptualization of AD turn out unequivocally to be for the better. Otherwise, the reconceptualization may do more harm than good.     

Neuroprotective and symptomatic effects of targeting group III mGlu receptors in neurodegenerative disease

Neurodegenerative disorders possess common pathological mechanisms, such as protein aggregation, inflammation, oxidative stress (OS) and excitotoxicity, raising the possibility of shared therapeutic targets. As a result of the selective cellular and regional expression of group III metabotropic glutamate (mGlu) receptors, drugs targeting such receptors have demonstrated both neuroprotective properties and symptomatic improvements in several models of neurodegeneration. In recent years, the discovery and development of subtype‐selective ligands for the group III mGlu receptors has gained pace, allowing further research into the functions of these receptors and revealing their roles in health and disease. Activation of this class of receptors results in neuroprotection, with a variety of underlying mechanisms implicated. Group III mGlu receptor stimulation prevents excitotoxicity by inhibiting glutamate release from neurons and microglia and increasing glutamate uptake by astrocytes. It also attenuates the neuroinflammatory response by reducing glial reactivity and encourages neurotrophic phenotypes. This article will review the current literature with regard to the neuroprotective and symptomatic effects of group III mGlu receptor activation and discuss their promise as therapeutic targets in neurodegenerative disease.

     

Regional distribution of tetrahydroisoquinoline derivatives in rodent,human, and parkinson’s disease brain

Several members of the tetrahydroisoquinoline (TIQ) family of monoamine alkaloids can be formed from dopamine or its oxidized metabolites and may be involved in the pathogenesis of monoaminergic cell death in Parkinson’s disease (PD). Using enantiomeric‐selective high‐performance liquid chromatography with electrochemical detection and liquid chromatography with tandem mass spectroscopy, the regional concentrations of several TIQ derivatives, including salsolinols, were determined in mouse, rat, normal human, and PD brain. TIQ derivatives were detected in all regions subjected to analysis. In general, salsolinols were present at higher concentrations than TIQ and its benzyl and methyl derivatives, especially in human brain. Moreover, salsolinols were concentrated in areas with increased dopamine synthesis and turnover such as the ventral midbrain and striatum, respectively. A possible consequence of nigrostriatal dopaminergic cell death, significantly lower levels of (R)salsolinol, (S)salsolinol, N‐methyl‐(R)salsolinol and N‐methyl‐(S)salsolinol were found in the caudate nuclei of PD in comparison with normal human brain. Our data support the hypothesis of endogenous synthesis of salsolinols and provide evidence for their accumulation in catecholaminergic neurons.     

Netrin‐1 and its receptor DCC modulate survival and death of dopamine neurons and Parkinson’s disease features

The netrin‐1/DCC ligand/receptor pair has key roles in central nervous system (CNS) development, mediating axonal, and neuronal navigation. Although expression of netrin‐1 and DCC is maintained in the adult brain, little is known about their role in mature neurons. Notably, netrin‐1 is highly expressed in the adult substantia nigra, leading us to investigate a role of the netrin‐1/DCC pair in adult nigral neuron fate. Here, we show that silencing netrin‐1 in the adult substantia nigra of mice induces DCC cleavage and a significant loss of dopamine neurons, resulting in motor deficits. Because loss of adult dopamine neurons and motor impairments are features of Parkinson’s disease (PD), we studied the potential impact of netrin‐1 in different animal models of PD. We demonstrate that both overexpression of netrin‐1 and brain administration of recombinant netrin‐1 are neuroprotective and neurorestorative in mouse and rat models of PD. Of interest, we observed that netrin‐1 levels are significantly reduced in PD patient brain samples. These results highlight the key role of netrin‐1 in adult dopamine neuron fate, and the therapeutic potential of targeting netrin‐1 signaling in PD.     

The role of nitric oxide signaling in renoprotective effects of hydrogen sulfide against chronic kidney disease in rats: Involvement of oxidative stress,autophagy and apoptosis

The interplay between H₂S and nitric oxide (NO) is thought to contribute to renal functions. The current study was designed to assess the role of NO in mediating the renoprotective effects of hydrogen sulfide in the 5/6 nephrectomy (5/6 Nx) animal model. Forty rats were randomly assigned to 5 experimental groups: (a) Sham; (b) 5/6 Nx; (c) 5/6Nx+sodium hydrosulfide-a donor of H ₂S, (5/6Nx+sodium hydrosulfide [NaHS]); (d) 5/6Nx+NaHS+ L -NAME (a nonspecific nitric oxide synthase [NOS] inhibitor); (e) 5/6Nx+NaHS+aminoguanidine (a selective inhibitor of inducible NOS [iNOS]). Twelve weeks after 5/6 Nx, we assessed the expressions of iNOS and endothelial NOS (eNOS), oxidative/antioxidant status, renal fibrosis, urine N-acetyl-b-glucosaminidase (NAG) activity as the markers of kidney injury and various markers of apoptosis, inflammation, remodeling, and autophagy. NaHS treatment protected the animals against chronic kidney injury as depicted by improved oxidative/antioxidant status, reduced apoptosis, and autophagy and attenuated messenger RNA (mRNA) expression of genes associated with inflammation, remodeling, and NAG activity. Eight weeks Nω-nitro-l-arginine methyl ester ( L -NAME) administration reduced the protective effects of hydrogen sulfide. In contrast, aminoguanidine augmented the beneficial effects of hydrogen sulfide. Our finding revealed some fascinating interactions between NO and H ₂S in the kidney. Moreover, the study suggests that NO, in an isoform-dependent manner, can exert renoprotective effects in 5/6 Nx model of CKD.     

Interleukin-6 in neuro-Behçet’s disease: Association with disease subsets and long-term outcome

Increased cerebrospinal fluid (CSF) IL-6 has been reported in patients with Behçet’s disease (BD) and neurological involvement. To elucidate the value of IL-6 as a marker of disease activity, serum and CSF IL-6 levels of 68 BD patients with acute (26) or chronic progressive (14) parenchymal involvement (pNB), dural sinus thrombosis (10), ischemic stroke (5) or headache (13) were measured by ELISA. Samples from multiple sclerosis, subacute sclerosing panencephalitis, and noninflammatory neurological disorders were used as controls. CSF but not serum samples of neuro-BD patients with acute pNB displayed significantly increased IL-6 levels as compared to other groups. Chronic progressive pNB patients also showed increased CSF IL-6 levels, albeit less prominent. Patients with increased CSF IL-6 levels were more likely to have increased CSF cell counts and total protein levels and these three parameters were correlated with long-term (3 years) disease outcome. In four chronic progressive patients, IL-6 was elevated despite otherwise normal CSF. CSF IL-6 seems to be a marker of disease activity and long-term outcome for pNB along with CSF cell count and protein levels. CSF IL-6 could be used in chronic progressive patients who have normal CSF cell, or protein levels to detect disease activity.