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1.
Parkinson’s disease (PD) is a chronic and progressive neurodegeneration of dopamine neurons in the substantia nigra. The reason for the death of these neurons is unclear; however, studies have demonstrated the potential involvement of mitochondria, endoplasmic reticulum, α-synuclein or dopamine levels in contributing to cellular oxidative stress as well as PD symptoms. Even though those papers had separately described the individual roles of each element leading to neurodegeneration, recent publications suggest that neurodegeneration is the product of various cellular interactions. This review discusses the role of oxidative stress in mediating separate pathological events that together, ultimately result in cell death in PD. Understanding the multi-faceted relationships between these events, with oxidative stress as a common denominator underlying these processes, is needed for developing better therapeutic strategies. 相似文献
2.
Parkinson’s disease (PD) is a neurodegenerative disorder, caused by reduced levels of catecholamines and oxidative stress. Symptoms seen in the disease include tremor, rigidity, bradykinesia and postural disability. Oxidative stress plays a key role in neurodegeneration and motor abnormalities seen in PD. Altered levels of the protein caused by these changes lead to defective ubiquitin–proteasome pathway. Neurodegeneration seen in PD and Canavan disease has a common mechanism. Recent studies suggest that herbal medicines can improve molecular changes and motor functions seen in PD. 相似文献
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4.
C. Pasetti S. Rossi Ferrario R. Fornara D. Picco C. Foglia J. Galli 《Neurological sciences》2003,24(3):203-204
Abstract.
Relatively little has been published in the international
literature concerning the caregiving-related problems associated
with Parkinsons disease. We therefore undertook two exploratory
studies that have allowed us to identify the needs and specific
problems perceived by such caregivers in both qualitative and
quantitative terms. 相似文献
5.
Lemke Matthias R. Fuchs Gerd Gemende Irene Herting Birgit Oehlwein Christian Reichmann Heinz Rieke Jrgen Volkmann Jens 《Journal of neurology》2004,251(6):vi24-vi27
Abstract.
Depression occurs in approximately 45% of all patients with Parkinsons disease (PD), reduces quality of life independent of motor symptoms and seems to be underrated and undertreated. Characteristics of symptoms differ from major depression. Because of overlapping clinical symptoms, diagnosis is based on subjectively experienced anhedonia and feeling of emptiness. Available rating scales for major depression may not be adequate to correctly measure severity of depression in PD. Anxiety and depression may manifest as first symptoms of PD many years before motor symptoms. Serotonergic, noradrenergic and dopaminergic mechanisms play key roles in the etiology of depression in PD. Tricyclic and newer, selective antidepressants including serotonin and noradrenaline reuptake inhibitors (SSRI, SNRI) appear to be effective in treating depression in PD. Selective reuptake inhibitors seem to have a favorable side effect profile. Recent controlled studies show antidepressant effects of pramipexole in bipolar II depression. New dopamine agonists pramipexole and ropinirole appear to ameliorate depressive symptoms in PD in addition to effects on motor symptoms. There is a lack of appropriate rating scales and controlled studies regarding depression in PD. 相似文献
6.
Rifampicin is a macrocyclic antibiotic used extensively for the treatment of Mycobacterium tuberculosis and other mycobacterial infections. Recently, it was discovered that rifampicin exhibits neuroprotective effects. It has been shown to protect PC12 cells against MPP+-induced apoptosis and inhibit the expression of α-synuclein multimers. In in vitro studies, rifampicin pretreatment protects PC12 cells against rotenone-induced cell death. Qualitative and quantitative analyses uncover that rifampicin significantly suppresses rotenone-induced apoptosis by ameliorating mitochondrial oxidative stress. It reduces microglial inflammation and improves neuron survival. Our results indicate that rifampicin is cytoprotective under a variety of experimental conditions, and suggest that it may be useful in PD therapeutics. It is the aim of this paper to review the experimental neuroprotection data reported using rifampicin with a focus on the molecular and cellular mechanisms of cytoprotective effect in in vitro models of PD. 相似文献
7.
The principal mechanism of the pathogenesis of Parkinson’s disease is accumulation and aggregation of alpha-synuclein. While the normal function of alpha-synuclein is the control of vesicular neurotransmission, its pathogenic effects influence different cell functions, including the activities of mitochondria and proteasomes, as well as autophagic protein degradation. It is noteworthy that the same functions are affected when the renewal of macromolecules and organelles is impaired as a result of normal aging. Since aging is the principal risk factor for Parkinson’s disease, it is very important to analyze its molecular and cellular consequences in the context of alpha-synuclein pathology. Here, we review the similarities and differences between normal brain aging and Parkinson’s disease, with a focus on nigral dopaminergic neurons, which seem to be specifically sensitive to the combined damage induced by alpha-synuclein and aging. Elucidating the mechanism that underlies the death of dopaminergic neurons in Parkinson’s disease is essential not only for the understanding of its general pathogenesis but also for the development of approaches to its early preclinical diagnosis and preventive therapy. 相似文献
8.
《中国神经再生研究》2012,7(17):1343
Totally three articles focusing on bone marrow mesenchymal stem cells alleviating PC12 cytotoxicity induced by 6-hydroxydopamine and intracerebroventricular transplantation of non-modified/gene-modified 相似文献
9.
《中国神经再生研究》2012,7(5):368
Totally three articles focusing on gene therapy of Parkinson’s disease, the effect of levodopa on toxicity of dopaminergic neurons in substantia nigra and striatum, and the effect of rifampicin on reducing Parkinson’s disease-induced dopaminergic neuronal apoptosis 相似文献
10.
Parkinson’s disease is a neurodegenerative disease characterised by a massive loss of dopaminergic neurons in the substantia nigra. Yet glial cells may also participate in the pathophysiology of the disease. Indeed, glial cells can produce trophic factors which may stimulate neuronal survival or, alternatively, they could produce toxic compounds which may be involved in neuronal degeneration. This paper reviews the potentially protective or deleterious effects of glial cells in the substantia nigra of patients with Parkinson’s disease.
相似文献11.
Lim Ee Wei Aarsland Dag Ffytche Dominic Taddei Raquel Natalia van Wamelen Daniel J. Wan Yi-Min Tan Eng King Ray Chaudhuri Kallol 《Journal of neurology》2019,266(11):2605-2619
Journal of Neurology - Parkinson’s disease (PD) is the second commonest neurodegenerative disorder in the world with a rising prevalence. The pathophysiology is multifactorial but aggregation... 相似文献
12.
William T. Hu Alice Chen-Plotkin Steven E. Arnold Murray Grossman Christopher M. Clark Leslie M. Shaw Leo McCluskey Lauren Elman Jason Karlawish Howard I. Hurtig Andrew Siderowf Virginia M.-Y. Lee Holly Soares John Q. Trojanowski 《Acta neuropathologica》2010,120(3):385-399
Ante-mortem diagnosis of neurodegenerative disorders based on clinical features alone is associated with variable sensitivity and specificity, and biomarkers can potentially improve the accuracy of clinical diagnosis. In patients suspected of having Alzheimer’s disease (AD), alterations in cerebrospinal fluid (CSF) biomarkers that reflect the neuropathologic changes of AD strongly support the diagnosis, although there is a trade-off between sensitivity and specificity due to similar changes in cognitively healthy subjects. Here, we review the current approaches in using CSF AD biomarkers (total tau, p-tau181, and Aβ42) to predict the presence of AD pathology, and our recent work using multi-analyte profiling to derive novel biomarkers for biofluid-based AD diagnosis. We also review our use of the multi-analyte profiling strategy to identify novel biomarkers that can distinguish between subtypes of frontotemporal lobar degeneration, and those at risk of developing cognitive impairment in Parkinson’s disease. Multi-analyte profiling is a powerful tool for biomarker discovery in complex neurodegenerative disorders, and analytes associated with one or more diseases may shed light on relevant biological pathways and potential targets for intervention. 相似文献
13.
Hikmet Can Çubukçu Mustafa Yurtdaş Zahide Esra Durak Bilal Aytaç Hafize Nalan Güneş Burcu Gökçe Çokal Tahir Kurtuluş Yoldaş İlker Durak 《Neurological sciences》2016,37(11):1793-1798
Parkinson’s disease (PD) is one of the common neurodegenerative disorders. Oxidative stress is considered as a contributing factor to the development of PD. The present study aims to investigate serum oxidative stress status in patients with PD. Oxidative stress was assessed by measuring serum nitric oxide levels, lipid hydroperoxide concentrations, and nitric oxide synthase activity. In addition, total serum antioxidant capacity (TAC) was evaluated using the serum 2,2-Diphenyl-1-picryl-hydrazyl (DPPH) free-radical scavenging method in 32 patient with Parkinson’s disease and 32 control subjects. Our results indicated that serum nitric oxide and lipid hydroperoxide levels were significantly lower in patients with PD than controls. Moreover, nitric oxide levels were found to be negatively correlated with Unified Parkinson’s Disease Rating Scale (UPDRS). However, no statistical difference was observed in total serum antioxidant capacities and nitric oxide synthase activities between patients and controls. The present study indicates that although antioxidant capacity was not changed, lipid hydroperoxide (LPO) level was found decreased. This might show pre-oxidative process in these patients. In addition, decreased nitric oxide (NO) level and negative correlation observed between NO level and disease rating scale implicated a role for NO in the disease process. 相似文献
14.
In vitro studies designed to probe the cellular mechanisms underlying β-amyloid (Aβ) toxicity in neurons have implicated several
processes, including hyperphosphorylation of the microtubule (MT)-associated protein tau, loss of MT stability, and increased cytosolic calcium levels. Given that Alzheimer's disease involves accumulation of aggregates
of two different proteins, the potential involvement of the unfolded protein response (UPR) and endoplasmic reticulum (ER)
dysfunction has been suggested to lead to cell death. The relationship between these apparently divergent factors and pathways
in Aβ toxicity is still unclear. In these studies we investigated the relationship between MT stability and the ER stress
response in primary neurons exposed to toxic Aβ peptides in culture. In addition, nocodazole (ND) was used to determine if
direct disruption of MT organization activated the UPR. Pretreatment of neurons with MT-stabilizing drugs paclitaxel (Taxol)
and epothilone A prevented the induction of three indicators of the UPR induced by Aβ, ND, and thapsigargin, a compound known
to inhibit the sarco-ER Ca2+-ATPase and deplete ER calcium stores, resulting in initiation of the UPR. In addition, treatment with MT-stabilizing drugs
blocked cell death and the cytoskeletal disorganization induced by these insults. The results suggest that loss of cytoskeletal
integrity is a very early step in the response to a variety of toxic stimuli and that preservation of MT stability might be
important in preventing the induction of ER dysfunction and subsequent cell death by Aβ in neurons. 相似文献
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16.
Aasef G. Shaikh 《Neurological sciences》2017,38(5):855-863
Parkinson’s disease, the most common cause of parkinsonism is often difficult to distinguish from its second most common etiology due to exposure to dopamine receptor blocking agents such as antiemetics and neuroleptics. Dual axis accelerometry was used to quantify tremor in 158 patients with parkinsonism; 62 had Parkinson’s disease and 96 were clinically diagnosed with dopamine receptor blocking agent-induced parkinsonism. Tremor was measured while subjects rested arms (resting tremor), outstretched arms in front (postural tremor), and reached a target (kinetic tremor). Cycle-by-cycle analysis was performed to measure cycle duration, oscillation amplitude, and inter-cycle variations in the frequency. Patients with dopamine receptor blocker induced parkinsonism had lower resting and postural tremor amplitude. There was a substantial increase of kinetic tremor amplitude in both disorders. Postural and resting tremor in subjects with dopamine receptor blocking agent-induced parkinsonism was prominent in the abduction–adduction plane. In contrast, the Parkinson’s disease tremor had equal amplitude in all three planes of motion. Tremor frequency was comparable in both groups. Remarkable variability in the width of the oscillatory cycles suggested irregularity in the oscillatory waveforms in both subtypes of parkinsonism. Quantitative tremor analysis can distinguish Parkinson’s disease from dopamine receptor blocking agent-induced parkinsonism. 相似文献
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18.
Objectives To determine
whether there are gender differences
in the Parkinson’s disease
(PD) phenotype using a large
clinic–based cohort.
Methods We
examined gender differences in demographic,
historical and clinical
characteristics in a consecutive
clinical series of 1264 individuals
diagnosed with PD.
Results The
majority of individuals in the sample
were male (67 %). Comparative
analyses showed males and females
were not significantly different on
most demographic and historical
characteristics. For both genders,
the mean age and the mean age at
symptomatic onset were about 70
and 63 years, respectively and, thus,
disease duration was not significantly
different between genders.
The proportion of individuals with
a positive family history of PD
(15 %) was similar for both genders.
A positive history of depression
was significantly higher in females
(35 % vs. 24 %). The UPDRS
instability score was significantly
worse among females, whereas the
rigidity score was significantly
worse for males. Females showed
significantly worse ADL capacity
and a more advanced H&Y stage.
The proportion of individuals receiving
antiparkinsonian medication
(about 66 %) and time between
the last dose and the clinical
evaluation (about 4 hours) was
similar for both genders. There was
a trend for lower daily levodopa
equivalence dosage and more severe
dyskinesia score among females
but these differences did not
reach statistical significance after
Bonferroni correction.
Conclusions The majority of comparisons
tended to highlight the commonalities
in the PD phenotype between
genders, particularly in reference
to historical and early disease stage
characteristics. However, gender
may be an important factor related
to the expression of PD features
during the symptomatic disease
course. 相似文献
19.
Richard IH 《Current neurology and neuroscience reports》2007,7(4):295-301
This article provides an update on depression and apathy in Parkinson’s disease (PD), both of which are common but often misunderstood.
The diagnosis of depression in PD can be challenging and we still do not have solid evidence on which to base our treatment
decisions. Apathy is most commonly seen in the setting of dementia or depression but emerging evidence suggests that it may
be a core feature of PD. There are conflicting reports about the effects of deep brain stimulation (DBS) on mood and apathy,
but studies suggest that at least some patients may develop depression and apathy after the procedure. Although we are making
strides toward a better understanding of depression and apathy in PD, it is clear that more research is needed about these
non-motor features. 相似文献
20.
Lubomski Michal Tan Ai Huey Lim Shen-Yang Holmes Andrew J. Davis Ryan L. Sue Carolyn M. 《Journal of neurology》2020,267(9):2507-2523
Journal of Neurology - Recently, there has been a surge in awareness of the gastrointestinal microbiome (GM) and its role in health and disease. Of particular note is an association between the GM... 相似文献