Abstract：
:Current concepts regarding the pathogenesis of Parkinson's disease support a model whereby environmental factors conspire with a permissive genetic background to initiate the disease. The identity of the responsible environmental trigger has remained elusive. There is incontrovertible evidence that aggregation of the neuronal protein alpha-synuclein is central to disease pathogenesis. A novel hypothesis of Parkinson's pathogenesis, articulated by Braak and colleagues, implicates a pathogen acting in the olfactory mucosa and gastrointestinal tract as the inciting agent. In this point-of-view article, we hypothesize that α-synuclein aggregation in Parkinson's disease is an Epstein-Barr virus (EBV)-induced autoimmune phenomenon. Specifically, we have shown evidence for molecular mimicry between the C-terminal region of α-synuclein and a repeat region in the latent membrane protein 1 encoded by EBV. We hypothesize that, in genetically-susceptible individuals, anti-EBV latent membrane protein antibodies targeting the critical repeat region cross react with the homologous epitope on α-synuclein and induce its oligomerization. Consistent with the Braak's proposed pattern of spread, we contend that axon terminals in the lamina propria of the gut are among the initial targets, with subsequent spread of pathology to the CNS. While at this time, we can only provide evidence from the literature and preliminary findings from our own laboratory, we hope that our hypothesis will stimulate the development of tractable experimental systems that can be exploited to test it. Further support for an EBV-induced immune pathogenesis for Parkinson's disease could have profound therapeutic implications.
journal_name
Parkinsonism Relat Disordjournal_title
Parkinsonism & related disordersauthors
Woulfe JM,Gray MT,Gray DA,Munoz DG,Middeldorp JMdoi
10.1016/j.parkreldis.2014.02.031subject
Has Abstractpub_date
2014-07-01 00:00:00pages
685-94issue
7eissn
1353-8020issn
1873-5126pii
S1353-8020(14)00091-1journal_volume
20pub_type
杂志文章,评审abstract：INTRODUCTION:Executive dysfunction is a common and early cognitive symptom in Parkinson's disease (PD) with a detrimental effect on quality of life of patients and their care givers. Thus, a number of neuroimaging studies investigated the underlying neural correlates of such an impairment. Results of individual studies...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章,meta分析
doi：10.1016/j.parkreldis.2019.02.015
更新日期：2019-06-01 00:00:00
abstract：OBJECTIVE:The object of the present study was to evaluate whether patients with neurolathyrism (NL) have cognitive abnormalities, and whether the cognitive decline, if found, correlates with the motor deficit. BACKGROUND:NL is a neurological syndrome that develops following ingestion of the grass pea (Lathyrus Sativus...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/s1353-8020(99)00016-4
更新日期：1999-04-01 00:00:00
abstract：:Levodopa is one of the most effective symptomatic treatment options for Parkinsonism with a favorable safety and tolerability profile. In some patients, particularly those suffering from orthostatic intolerance, the hypotensive effect of levodopa limits its therapeutic use. We used continuous noninvasive cardiovascula...
journal_title：Parkinsonism & related disorders
pub_type： 临床试验,杂志文章
doi：10.1016/j.parkreldis.2014.04.007
更新日期：2014-08-01 00:00:00
abstract：:Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. An association with sleep breathing disorder has not previously been established in the literature. We report the case of a 45-year-old woman with HD, presenting with snoring and observed apnea. Polysomnography showed obstructive sleep apne...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/j.parkreldis.2005.01.005
更新日期：2005-06-01 00:00:00
abstract：BACKGROUND:The prevalence and clinical correlates of drooling in Chinese patients with Parkinson disease (PD) are unknown. METHODS:A cross-sectional analysis of 518 Chinese patients with PD was conducted. Assessments included Unified PD Rating Scale (UPDRS), Non-Motor Symptoms Scale (NMSS), Hamilton Depression Scale (...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/j.parkreldis.2014.12.004
更新日期：2015-03-01 00:00:00
abstract：:Essential tremor (ET) is among the common movement disorders. A surge in research in recent years has considerably improved our understanding of disease etiology and pathogenesis, and its associated clinical phenomenology and natural history. With this progress have emerged a multitude of new questions and conundrums ...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/j.parkreldis.2020.10.035
更新日期：2020-12-01 00:00:00
abstract：:A previously healthy 10-year-old girl developed a right hemiparesis with sensory loss secondary to a posterolateral thalamic infarct. Despite improvement in strength, three weeks later a 4 Hz kinetic tremor appeared in the right hand accompanied by dystonia in the right upper and lower limbs. Basal ganglia vascular le...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/s1353-8020(98)00029-7
更新日期：1998-10-01 00:00:00
abstract：:Six healthy controls and eighteen patients with Parkinson's disease in different disability stages were studied with SPECT using [(123)I]beta-CIT to label the striatal dopamine transporter. The mean uptake of [(123)I]beta-CIT in the putamen was reduced to 54% of the control mean and to 65% of the average control value...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/1353-8020(95)00012-u
更新日期：1995-07-01 00:00:00
abstract：INTRODUCTION:somatosensory temporal discrimination threshold (STDT) measures the ability to perceive two stimuli as being sequential. Altered STDT has been reported in Parkinson's disease (PD). The cerebellum seems to play a role in the pathophysiology of PD, and may consequently be involved in the pathophysiology of S...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/j.parkreldis.2015.04.004
更新日期：2015-07-01 00:00:00
abstract：:Parkinson's disease (PD) is a common neurodegenerative disorder of unknown cause. For decades, a deficit in mitochondrial respiration was thought to be a key factor in PD neurodegeneration. However, excluding a few exceptions where a clinical picture of parkinsonism is associated with a mitochondrial DNA mutation, pre...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/S1353-8020(09)70823-5
更新日期：2009-12-01 00:00:00
abstract：INTRODUCTION:We sought to assess the effect of subthalamic deep brain stimulation (STN DBS) on Parkinson's disease (PD)-associated postural abnormalities. METHODS:A computerized analysis of posture was used to quantify the thoracolumbar, thoracic, and cervical-occipital ventral angles, as well as the thoracolumbar and...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/j.parkreldis.2019.01.003
更新日期：2019-05-01 00:00:00
abstract：:The immunohistochemical demonstration of reactive microglia and activated complement components suggests that chronic inflammation occurs in affected brain regions in Parkinson's disease (PD). Evidence from humans and monkeys exposed to MPTP indicates this inflammation may persist many years after the initial stimulus...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章,评审
doi：10.1016/j.parkreldis.2004.01.005
更新日期：2004-05-01 00:00:00
abstract：:A confluence of variables in Parkinson's disease results in Parkinson's informal caregivers facing tremendous challenges. Factors include: motor and non-motor symptoms, staging, rate of progression and increased life expectancy of people with Parkinson's (PwP) due to effective drug therapy and surgery. Informal caregi...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/S1353-8020(09)70796-5
更新日期：2009-12-01 00:00:00
abstract：BACKGROUND:In addition to the most frequent TOR1A/DYT1 mutation (c.907_909delGAG), a growing number of TOR1A sequence variants are found in dystonia patients. For most, functional characterization has demonstrated pathogenicity at different levels, implying that TOR1A genetic testing should not be limited to screening ...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/j.parkreldis.2015.08.001
更新日期：2015-10-01 00:00:00
abstract：INTRODUCTION:Germline silencing of the PD-related protein LRRK2 does not alter glutamate or dopamine release in adult mice, but some exploratory abnormalities have been reported with ageing. Contrastingly, high levels of human LRRK2 cause locomotor alterations and cognitive deficits accompanied by reduced striatal dopa...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/j.parkreldis.2015.07.025
更新日期：2015-10-01 00:00:00
abstract：:We report here on a Japanese family in which five members in three generations developed non-progressive adult onset cortical tremor and epilepsy. Other than tremulous movements resembling essential tremor, the neurologic findings were unremarkable. Electrophysiologic studies revealed giant somatosensory evoked potent...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/s1353-8020(97)00001-1
更新日期：1997-04-01 00:00:00
abstract：INTRODUCTION:Inconsistent results regarding the association between the components of metabolic syndrome and Parkinson's disease (PD) have been reported. We investigated whether the metabolic syndrome or its components, or serum total cholesterol, predict PD incidence in a prospective cohort study design. METHODS:The ...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/j.parkreldis.2015.07.017
更新日期：2015-10-01 00:00:00
abstract：OBJECTIVES:Compare the efficacy of two walking assistance devices (wheeled walker and standard walker) to unassisted walking for patients with PD and gait freezing. BACKGROUND:Although numerous walking devices are used clinically, their relative effects on freezing and walking speed have never been systematically test...
journal_title：Parkinsonism & related disorders
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1016/s1353-8020(03)00060-9
更新日期：2003-10-01 00:00:00
abstract：BACKGROUND:Deep brain stimulation improves motor function and quality of life in patients with Parkinson's disease. The impact of these changes on patients' spouses is largely unknown. METHODS:Twenty-six spouses of patients undergoing surgery were evaluated before and 12 months after surgery, using the 36-Item Short F...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/j.parkreldis.2011.11.008
更新日期：2012-06-01 00:00:00
abstract：:Several changes to society in the last four decades have had implications for people and their families living with Parkinson's disease (PD): (1) The change in the role of voluntary organisations highlighting the importance of listening to the needs of the patients and their families. (2) Demographic changes resulting...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章,评审
doi：10.1016/S1353-8020(08)70056-7
更新日期：2007-01-01 00:00:00
abstract：OBJECTIVE:To evaluate the subject-investigator agreement on the Unified Parkinson's Disease Rating Scale (UPDRS) subsections I and II. METHODS:Subject-investigator agreement was estimated at baseline and endpoint by Kappa statistics for individual items and concordance correlations for subscale totals using data from ...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/j.parkreldis.2011.10.006
更新日期：2012-03-01 00:00:00
abstract：:Synchronization of neuronal activity within and across distributed brain regions is a fundamental property of cortical and subcortical networks and serves a variety of functions including motor and cognitive processes. Data will be reviewed here from cross-sectional EEG and MEG studies to suggest that Parkinson's dise...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章,评审
doi：10.1016/S1353-8020(08)70046-4
更新日期：2007-01-01 00:00:00
abstract：:Primary monogenic forms of dystonia manifest solely or mainly with dystonia; they have been linked to a number of genes and loci and assigned "DYT" numbers. The pure dystonia syndrome early-onset primary dystonia (DYT1) manifests with dominantly-inherited generalized dystonia, often with focal onset in a limb. DYT1 is...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章,评审
doi：10.1016/S1353-8020(11)70049-9
更新日期：2012-01-01 00:00:00
abstract：OBJECTIVE:Invasive techniques such as in-vivo microdialysis provide the opportunity to directly assess neurotransmitter levels in subcortical brain areas. METHODS:Five male Filipino patients (mean age 42.4, range 34-52 years) with severe X-linked dystonia-parkinsonism underwent bilateral implantation of deep brain lea...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/j.parkreldis.2015.06.010
更新日期：2015-08-01 00:00:00
abstract：INTRODUCTION:Patients with Parkinson disease (PD) and their partners may experience a worsening of their sexual life. AIM:To assess quality of sexual life (QoSL) in male and female PD patients and their partners. MATERIALS AND METHODS:Medical, demographic and clinical data was collected regarding consecutive PD patie...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/j.parkreldis.2014.07.003
更新日期：2014-10-01 00:00:00
abstract：:Abnormally aggregated tau protein is central to the pathophysiology of Alzheimer's disease, frontotemporal dementia variants, progressive supranuclear palsy, corticobasal degeneration and chronic traumatic encephalopathy. The post-mortem cortical density of hyperphosphorylated tau tangles correlates with pre-morbid co...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章,评审
doi：10.1016/j.parkreldis.2015.08.011
更新日期：2016-01-01 00:00:00
abstract：BACKGROUND:The Montreal Cognitive Assessment (MoCA) is increasingly being used as a cognitive screening test in Parkinson disease (PD). The MoCA's popularity likely reflects its ability to detect executive dysfunction, a relative deficiency of the Mini-Mental State Examination (MMSE). OBJECTIVE:To compare neurochemica...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/j.parkreldis.2014.07.008
更新日期：2014-10-01 00:00:00
abstract：:Parkinson's disease (PD) patients have a ninefold increased risk of recurring falls compared to healthy controls. The risk of falling due to cardiovascular dysautonomia (CVD) is not quantifiable. But, CVD is an integral part of the disease and at least 20% of PD patients suffer from orthostatic hypotension, an express...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章,评审
doi：10.1016/j.parkreldis.2006.02.001
更新日期：2006-05-01 00:00:00
abstract：:We report on two cases who presented with involuntary facial grimacing and frowning. Blepharospasm has never been documented in one, and the other case showed difficulty in lid opening only in the early phase of the disease. Botulinum toxin was effective for both. This is a hitherto unreported presentation of upper fa...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/j.parkreldis.2007.12.001
更新日期：2008-11-01 00:00:00
abstract：BACKGROUND:Clinical differentiation between parkinsonian syndromes (PS) remains a challenge despite well-established clinical diagnostic criteria. Specific diagnostic biomarkers have yet to be identified, though in recent years, studies have been published on the aid of certain brain related proteins (BRP) in the diagn...
journal_title：Parkinsonism & related disorders
pub_type： 杂志文章
doi：10.1016/j.parkreldis.2011.08.012
更新日期：2012-01-01 00:00:00
