Abstract:
:Mutations in LRRK2 are the most common genetic cause of Parkinson's disease (PD). The most prevalent LRRK2 mutation is the G2019S coding change, located in the kinase domain of this complex multi-domain protein. The majority of G2019S autopsy cases feature typical Lewy Body pathology with a clinical phenotype almost indistinguishable from idiopathic PD (iPD). Here we have investigated the biochemical characteristics of α-synuclein in G2019S LRRK2 PD post-mortem material, in comparison to pathology-matched iPD. Immunohistochemistry with pS129 α-synuclein antibody showed that the medulla is heavily affected with pathology in G2019S PD whilst the basal ganglia (BG), limbic and frontal cortical regions demonstrated comparable pathology scores between G2019S PD and iPD. Significantly lower levels of the highly aggregated α-synuclein species in urea-SDS fractions were observed in G2019S cases compared to iPD in the BG and limbic cortex. Our data, albeit from a small number of cases, highlight a difference in the biochemical properties of aggregated α-synuclein in G2019S linked PD compared to iPD, despite a similar histopathological presentation. This divergence in solubility is most notable in the basal ganglia, a region that is affected preclinically and is damaged before overt dopaminergic cell death.
journal_name
Neurobiol Disjournal_title
Neurobiology of diseaseauthors
Mamais A,Raja M,Manzoni C,Dihanich S,Lees A,Moore D,Lewis PA,Bandopadhyay Rdoi
10.1016/j.nbd.2013.05.017subject
Has Abstractpub_date
2013-10-01 00:00:00pages
183-90eissn
0969-9961issn
1095-953Xpii
S0969-9961(13)00159-9journal_volume
58pub_type
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journal_title:Neurobiology of disease
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journal_title:Neurobiology of disease
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journal_title:Neurobiology of disease
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journal_title:Neurobiology of disease
pub_type: 杂志文章
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更新日期:2001-06-01 00:00:00
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journal_title:Neurobiology of disease
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doi:10.1016/j.nbd.2014.01.013
更新日期:2014-05-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2019.03.004
更新日期:2019-07-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2018.10.016
更新日期:2019-04-01 00:00:00
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pub_type: 杂志文章
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/s0969-9961(03)00131-1
更新日期:2003-11-01 00:00:00
abstract::Although there are no proven ways to delay onset or slow progression of Alzheimer's disease (AD), studies suggest that diet can affect risk. Pomegranates contain very high levels of antioxidant polyphenolic substances as compared to other fruits and vegetables. Polyphenols have been shown to be neuroprotective in diff...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2006.08.006
更新日期:2006-12-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2006.07.013
更新日期:2006-11-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2014.03.002
更新日期:2014-07-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2011.08.011
更新日期:2012-01-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2013.03.010
更新日期:2013-07-01 00:00:00
abstract::Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized behaviorally by chorea, incoordination, and shortened lifespan and neuropathologically by huntingtin inclusions and neuronal degeneration. In order to facilitate studies of pathogenesis and therapeutics, we have generated a new...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.07.014
更新日期:2006-02-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.02.005
更新日期:2005-10-01 00:00:00
abstract:BACKGROUND:Traumatic brain injury (TBI) causes 10-20% of acquired epilepsy, which typically develops within 2 years post-injury with poorly understood mechanisms. We investigated the location, severity, evolution and persistence of blood-brain barrier (BBB) dysfunction and associated neuroinflammation after TBI, and th...
journal_title:Neurobiology of disease
pub_type: 杂志文章
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2010.03.021
更新日期:2010-09-01 00:00:00
abstract::The mechanism of status epilepticus-induced neuronal death in the immature brain is not fully understood. In the present study, we examined the contribution of caspases in our lithium-pilocarpine model of status epilepticus in 14 days old rat pups. In CA1, upregulation of caspase-8, but not caspase-9, preceded caspase...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2009.10.019
更新日期:2010-02-01 00:00:00
abstract::The epsilon4 allele of the apolipoprotein E gene (APOE) is associated with sporadic and familial late-onset Alzheimer's disease (AD). Oxidative stress is believed to play an important role in neuronal dysfunction and cell death in AD. We now provide evidence that in the hippocampus of AD, the level of thiobarbituric a...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.1999.0273
更新日期:2000-02-01 00:00:00
abstract::Charcot-Marie-Tooth disease is a commonly inherited form of neuropathy. Although named over 100 years ago, identification of subtypes of Charcot-Marie-Tooth has rapidly expanded in the preceding decades with the advancement of genetic sequencing, including type 2F (CMT2F), due to mutations in heat shock protein 27 (Hs...
journal_title:Neurobiology of disease
pub_type: 杂志文章,评审
doi:10.1016/j.nbd.2019.104505
更新日期:2019-10-01 00:00:00
abstract::Several lines of evidence indicate that glutamate plays a crucial role in the initiation of seizures and their propagation; abnormal glutamate release causes synchronous firing of large populations of neurons, leading to seizures. In the present study, we investigated whether enhanced glutamate uptake by increased gli...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2012.03.032
更新日期:2012-08-01 00:00:00
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journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2019.104618
更新日期:2020-02-01 00:00:00
abstract::Both fragile X mental retardation protein (FMRP) and brain-derived neurotrophic factor (BDNF) are implicated in the maturation of neurons and in the higher cognitive functions. We have investigated whether FMRP and BDNF are reciprocally regulated in neurons. Exposure of cultured hippocampal neurons to BDNF, but not to...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1006/nbdi.2002.0544
更新日期:2002-10-01 00:00:00
abstract::Both the cellular prion protein (PrP(c)) and the amyloid precursor protein (APP) are physiologically subjected to complex proteolytic processing events. While for APP the proteinases involved--alpha-, beta- and gamma-secretase--have been identified in vitro and in vivo, the cleavage of PrP(c) by now has been linked on...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2009.07.015
更新日期:2009-11-01 00:00:00
abstract::Photoreceptor cell death is an irreversible, pathologic event in many blinding retinal diseases including retinitis pigmentosa, age-related macular disease, and retinal detachment. Light exposure can exacerbate a variety of human retinal diseases by increasing the rate of photoreceptor cell death. In the present study...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2005.08.017
更新日期:2006-03-01 00:00:00
abstract::Alzheimer's disease (AD) involves changes in both lipid and RNA metabolism, but it remained unknown if these differences associate with AD's cognition and/or post-mortem neuropathology indices. Here, we report RNA-sequencing evidence of inter-related associations between lipid processing, cognition level, and AD neuro...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2017.06.008
更新日期:2017-10-01 00:00:00
abstract::Over 1250 mutations in SCN1A, the Nav1.1 voltage-gated sodium channel gene, are associated with seizure disorders including GEFS+. To evaluate how a specific mutation, independent of genetic background, causes seizure activity we generated two pairs of isogenic human iPSC lines by CRISPR/Cas9 gene editing. One pair is...
journal_title:Neurobiology of disease
pub_type: 杂志文章
doi:10.1016/j.nbd.2019.104627
更新日期:2020-02-01 00:00:00