Abstract:
:Parkinson's disease (PD) is the second most common neurodegenerative disease. Mutations in Leucine-rich-repeat-kinase 2 (LRRK2), the causative gene for PARK8 type PD with autosomal dominant inheritance, are the most prevalent genetic causes of both familial and sporadic PD. Animal models are critical tools in the attempt to understand the mechanisms of LRRK2-mediated pathogenesis. We have generated human Bacterial Artificial Chromosome (BAC) mediated transgenic mouse models expressing mutant LRRK2 that robustly recapitulate the behavioral, neurochemical and pathological features of PD. These mice develop an age-dependent decrease in motor activity that is progressive and responds to treatment with levodopa. Pathologically, the most salient phenotype is early axonopathy of nigrostriatal dopaminergic neurons, accompanied by hyperphosphorylated tau. The mice also exhibit a consistent dopamine transmission deficit in both acute brain slices and live freely moving animals. Here we will discuss LRRK2 mouse models from several laboratories, their commonalities and differences, and offer scientific insights drawn from these studies.
journal_name
Parkinsonism Relat Disordjournal_title
Parkinsonism & related disordersauthors
Xu Q,Shenoy S,Li Cdoi
10.1016/S1353-8020(11)70058-Xsubject
Has Abstractpub_date
2012-01-01 00:00:00pages
S186-9eissn
1353-8020issn
1873-5126pii
S1353-8020(11)70058-Xjournal_volume
18 Suppl 1pub_type
杂志文章,评审abstract:INTRODUCTION:The age of diagnosis of Huntington's disease (HD) varies among individuals with the same HTT CAG-repeat expansion size. We investigated whether early-life events, like perinatal insults or neurodevelopmental disorders, influence the diagnosis age. METHODS:We used data from 13,856 participants from REGISTR...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章,多中心研究
doi:10.1016/j.parkreldis.2018.05.016
更新日期:2018-10-01 00:00:00
abstract:BACKGROUND:Somatosensory abnormalities contribute to the pathophysiology of Parkinson's disease (PD). The goal of this study was to identify abnormalities in the tactile-evoked activation of the somatosensory and motor cortices in PD, and in a sensorimotor circuit that traverses both of these cortical loci. The second ...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/j.parkreldis.2018.05.002
更新日期:2018-08-01 00:00:00
abstract:BACKGROUND:Non-motor symptoms (NMS) are common in Parkinson's disease (PD) and cause significant distress. A high rate of non-declaration of NMS by patients to healthcare providers (HCP) means that many NMS remain untreated. Current understanding of the factors preventing disclosure of NMS to HCPs is limited. The prese...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/j.parkreldis.2019.04.014
更新日期:2019-07-01 00:00:00
abstract::The interactive effects of neonatal iron and adult MPTP treatment groups of C57 Bl/6 mice were studied through adminustration of iron (Fe(2+)) 7.5mg/kg b.w., p.o. or vehicle (saline) on days 10-12 post partum, followed at 3months of age by administration of either MPTP (2x20 or 2x40mg/kg, s.c.) or saline. Neonatal iro...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/s1353-8020(00)00028-6
更新日期:2001-04-01 00:00:00
abstract::White matter lesions (WML) and epilepsy have been occasionally seen in Wilson's disease. No cases of generalized myoclonus have been reported so far. We present a patient with psychiatric symptoms starting at age 16, followed by tremor, generalized dystonia and severe generalized myoclonus. In addition to classical fi...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/j.parkreldis.2006.03.012
更新日期:2007-04-01 00:00:00
abstract:INTRODUCTION:Psychosis is one of the common non-motor symptoms of PD, which substantially worsens the quality of life. Hence, it is important to identify factors that are associated with early onset of psychosis in PD. In order to identify those factors, the current study aims to compare various demographic and clinica...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/j.parkreldis.2017.09.015
更新日期:2017-11-01 00:00:00
abstract:INTRODUCTION:The pathophysiology of dysphagia in Parkinson's disease (PD) is heterogeneous and poorly understood at present. This study investigated the phenotypes, prevalence and pathophysiology of oropharyngeal freezing (OPF) in PD and its relation to dysphagia. METHODS:In a prospective study, 50 PD patients were sy...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/j.parkreldis.2020.05.002
更新日期:2020-06-01 00:00:00
abstract:INTRODUCTION:The diagnosis of progressive supranuclear palsy is often challenging early in the course of the disease, when clinical signs of the condition may be less apparent and patients do not clearly meet diagnostic criteria. In this study, we examine a potential radiographic marker in progressive supranuclear pals...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/j.parkreldis.2016.05.006
更新日期:2016-07-01 00:00:00
abstract::Patients with idiopathic Parkinson's disease (PD) have impaired sympathetically mediated neurocirculatory innervation. Here we analyzed the correlation between cardiac (123)I-metaiodobenzylguanidine (MIBG) uptake, orthostatic hypotension and heart rate variability in treated patients with PD. Orthostatic hypotension (...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/j.parkreldis.2008.04.031
更新日期:2009-02-01 00:00:00
abstract:BACKGROUND:Survival in patients with Parkinson's disease is reduced as compared to the general population. We aimed to identify motor and non-motor features that predict mortality in Parkinson's disease. METHODS:A broad range of motor and non-motor features were assessed in a hospital-based cohort of 414 patients with...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/j.parkreldis.2014.02.030
更新日期:2014-06-01 00:00:00
abstract::The ataxias are a group of progressive neurodegenerative disorders with ataxia as the leading symptom. Current classifications distinguish between hereditary and non-hereditary ataxias. The hereditary ataxias are further divided into the autosomal recessive ataxias, the most frequent of which is Friedreich's ataxia, a...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章,评审
doi:10.1016/S1353-8020(08)70036-1
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:Cognitive impairment can occur in the early phase of Parkinson's disease and increases the risk of developing dementia. Cognitive deficits were shown to be associated with functional alterations in the dorsolateral prefrontal cortex (DLPFC) and caudate nucleus. Two previous transcranial magnetic stimulatio...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.parkreldis.2019.07.006
更新日期:2019-09-01 00:00:00
abstract::The aim of this study was to assess the middle latency auditory evoked potential (MLAEP) findings in idiopathic Parkinson's disease (IPD) and in patients who are regarded as having atypical parkinsonian disorders (AP) and to determine whether MLAEPs could contribute to the differential diagnosis of IPD and AP.MLAEPs w...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/s1353-8020(99)00056-5
更新日期:2000-04-01 00:00:00
abstract::The H1 haplotype was first identified 10 years ago. Initially, a dinucleotide polymorphism was detected in the tau (MAPT) gene and was subsequently found to be in linkage disequilibrium (LD) with other polymorphisms, forming the MAPT H1 haplotype, a risk factor for many neurological diseases, considered as tauopathies...
journal_title:Parkinsonism & related disorders
pub_type: 历史文章,杂志文章,评审
doi:10.1016/j.parkreldis.2008.03.001
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:No effective treatment for tardive dystonia (TD) has been well established. Deep brain stimulation (DBS) can ameliorate motor manifestations in primary dystonia, and may also be an effective approach for TD. OBJECTIVES:This study aimed to illuminate the long-term efficacy and safety of subthalamic nucleus (...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/j.parkreldis.2017.05.010
更新日期:2017-08-01 00:00:00
abstract::The adenosine A2A receptor is a major target of caffeine, the most widely used psychoactive substance worldwide. Large epidemiological studies have long shown caffeine consumption is a strong inverse predictor of Parkinson's disease (PD). In this review, we first examine the epidemiology of caffeine use vis-à-vis PD a...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/j.parkreldis.2020.10.024
更新日期:2020-11-01 00:00:00
abstract::Several factors involved in the etiology of Parkinson's disease (PD) have been proposed, including genetic and environmental factors or even a combination of both. Thus, multiple cellular hits are likely to contribute to neurodegeneration in PD. If such a mechanism happens to occur, our therapeutic intervention may pe...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章,评审
doi:10.1016/S1353-8020(08)70026-9
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:In late stage Parkinson patients there is an unmet need for new treatments to adequately control motor complications, especially dyskinesias. In several preliminary studies, it has been suggested that applying unilateral low-frequency repetitive transcranial magnetic stimulation (LF rTMS), delivered at the p...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/j.parkreldis.2015.11.009
更新日期:2016-01-01 00:00:00
abstract::Orthostatic hypotension is common in Parkinsonian patients. It is probably caused by reduced noradrenaline (NA) release. This effect is further enhanced by therapeutic use of ergot alkaloid dopamine agonists. In this trial we studied the impact of the non-ergot dopamine agonist ropinirole on blood pressure and noradre...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/s1353-8020(98)00014-5
更新日期:1998-08-01 00:00:00
abstract:BACKGROUND:Non-motor symptoms in Parkinson's disease (PD), such as cognitive, emotional, autonomic and somatosensory alterations, are not ubiquitous but vary between the tremor dominant (TD) and postural instability/gait difficulty (PIGD) subtypes of the syndrome. Non-motor phenomena (e.g., anxiety, depression and apat...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/j.parkreldis.2018.05.001
更新日期:2018-08-01 00:00:00
abstract:BACKGROUND:Multiple system atrophy (MSA) can clinically be divided into the cerebellar (MSA-C) and the parkinsonian (MSA-P) variants. It is unknown whether the variation in clinical expression is also reflected by a different underlying neurochemical profile. METHODS:We analyzed brain specific proteins and neurotransm...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/j.parkreldis.2007.02.002
更新日期:2007-12-01 00:00:00
abstract:INTRODUCTION:The deep brain stimulation (DBS) withdrawal syndrome (DBS-WDS) is a rare, life-threatening complication in Parkinson's disease (PD) patients with long disease duration and stimulation when stimulation is terminated for extended periods mostly due to infection of the DBS-hardware. METHODS, RESULTS:In five ...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/j.parkreldis.2018.06.035
更新日期:2018-11-01 00:00:00
abstract::The Behavioural Assessment of the Dysexecutive Syndrome (BADS) is a neuropsychological battery developed with the intent of measuring a wide range of executive impairments. Although the psychometric characteristics of BADS have previously been investigated in distinct neurological disorders, data on its validity in Pa...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/j.parkreldis.2009.07.011
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:Parkinson's disease patients may be at increased risk of delirium and developing adverse outcomes, such as cognitive decline and increased mortality. Delirium is an acute state of confusion that has overlapping symptoms with Parkinson's dementia, making it difficult to identify. This study aimed to determine...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/j.parkreldis.2018.09.025
更新日期:2019-07-01 00:00:00
abstract:OBJECTIVE:To determine the nationwide prevalence of primary dystonia, ataxia and hereditary spastic paraplegia (HSP) in Sweden. METHODS:We extracted data on all patients who were registered in The National Patient Register (NPR) in Sweden (population 9.64 million) at least twice during five consecutive years with a di...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/j.parkreldis.2019.10.028
更新日期:2019-12-01 00:00:00
abstract::The pedunculopontine nucleus (PPN) is a brainstem locomotive center that also processes sensory and behavioral information. Through its connections with basal ganglia structures and the spinal cord, the PPN may play a role in axial motor symptoms in Parkinson's disease (PD). We review the anatomical features of the PP...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章,评审
doi:10.1016/S1353-8020(08)70016-6
更新日期:2007-01-01 00:00:00
abstract::It has become increasingly apparent that Parkinson's disease (PD) can no longer be considered purely a motor disease, as numerous sensory alterations accompany this disorder either before or early in its clinical progression. Most notable among such disturbances are decrements in smell function. Such anomalies have be...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章,评审
doi:10.1016/S1353-8020(08)70006-3
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:The reduction of background activity and the increase of low-frequency powers on electroencephalogram (EEG) correlate with cognitive impairment and have been suggested to be underpinned by cholinergic deficit. We aimed to investigate the ratio between α and θ band power (α/θ ratio), as a synoptic index of ...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/j.parkreldis.2020.05.007
更新日期:2020-06-01 00:00:00
abstract::Some procedures, such as deep inspiration, increase sweat output (SSwR; sympathetic sweat response) and reduce cutaneous blood flow (SVR; skin vasomotor reflex) on the palm. We investigated SSwR, SVR, and cardiovascular function in 12 patients with progressive supranuclear palsy (PSP), 13 patients with Parkinson's dis...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章
doi:10.1016/s1353-8020(03)00109-3
更新日期:2003-12-01 00:00:00
abstract::The authors review some particularities of movement disorders (MDs) in the ethnically diverse population of Latin America. Although idiopathic diseases are evenly prevalent, access to treatment encounters difficulties that are worth discussing. Infectious-parasitic diseases observed throughout the continent occasional...
journal_title:Parkinsonism & related disorders
pub_type: 杂志文章,评审
doi:10.1016/j.parkreldis.2005.08.009
更新日期:2006-04-01 00:00:00