Abstract:
AIM:Peroxisomes play a key role in lipid metabolism, and peroxisome defects have been associated with neurodegenerative diseases such as X-adrenoleukodystrophy and Alzheimer's disease. This study aims to elucidate the contribution of peroxisomes in lipid alterations of area 8 of the frontal cortex in the spectrum of TDP43-proteinopathies. Cases of frontotemporal lobar degeneration-TDP43 (FTLD-TDP), manifested as sporadic (sFTLD-TDP) or linked to mutations in various genes including expansions of the non-coding region of C9ORF72 (c9FTLD), and of sporadic amyotrophic lateral sclerosis (sALS) as the most common TDP43 proteinopathies, were analysed. METHODS:We used transcriptomics and lipidomics methods to define the steady-state levels of gene expression and lipid profiles. RESULTS:Our results show alterations in gene expression of some components of peroxisomes and related lipid pathways in frontal cortex area 8 in sALS, sFTLD-TDP and c9FTLD. Additionally, we identify a lipidomic pattern associated with the ALS-FTLD-TDP43 proteinopathy spectrum, notably characterised by down-regulation of ether lipids and acylcarnitine among other lipid species, as well as alterations in the lipidome of each phenotype of TDP43 proteinopathy, which reveals commonalities and disease-dependent differences in lipid composition. CONCLUSION:Globally, lipid alterations in the human frontal cortex of the ALS-FTLD-TDP43 proteinopathy spectrum, which involve cell membrane composition and signalling, vulnerability against cellular stress and possible glucose metabolism, are partly related to peroxisome impairment.
journal_name
Neuropathol Appl Neurobioljournal_title
Neuropathology and applied neurobiologyauthors
Andrés-Benito P,Gelpi E,Jové M,Mota-Martorell N,Obis È,Portero-Otin M,Povedano M,Pujol A,Pamplona R,Ferrer Idoi
10.1111/nan.12681subject
Has Abstractpub_date
2020-12-17 00:00:00eissn
0305-1846issn
1365-2990pub_type
杂志文章abstract:AIMS:Population-based studies have shown that approximately 20% of the ageing population (aged 65 years and over) with dementia have little or no classical Alzheimer-type neuropathology. Cumulative DNA damage and a reduced capacity of DNA repair may result in neuronal dysfunction and contribute to cognitive impairment ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12202
更新日期:2015-06-01 00:00:00
abstract::The development of granule cells and the formation of synapses with mossy fibres were investigated in cerebella from jaundiced (j/j) Gunn rats with hereditary hyperbilirubinemia. The external granular layer was thinner than that in cerebella from heterozygous (+/j) Gunn rats without hyperbilirubinemia on days 12 and 1...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1993.tb00445.x
更新日期:1993-08-01 00:00:00
abstract::Creutzfeldt-Jakob disease (CJD) is characterized by a loss of neurons accompanied by astrogliosis and spongiform changes in the neuropil. It has been recognized that reactive microglia occur in CJD but little is known about the regional distribution and extent of the microglial activation. We have, therefore, examined...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1995.tb01097.x
更新日期:1995-12-01 00:00:00
abstract:AIM:Borna disease virus (BDV) induces a persistent infection in the central nervous system (CNS) accompanied by a non-purulent meningoencephalitis. BDV-infection of Lewis rats provides an important model to investigate basic principles of neurotropism, viral persistence and resulting dysfunctions. To date, the in vivo ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2008.00940.x
更新日期:2008-12-01 00:00:00
abstract:AIMS:Glioblastomas are highly aggressive and treatment resistant. Increasing evidence suggests that tumour-associated macrophages/microglia (TAMs) facilitate tumour progression by acquiring a M2-like phenotype. Our objective was to investigate the prognostic value of TAMs in gliomas using automated quantitative double ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12428
更新日期:2018-02-01 00:00:00
abstract::The causes of most neurological disorders are not fully understood. Inflammation and blood-brain barrier dysfunction appear to play major roles in the pathology of these diseases. Inflammatory insults that occur during brain development may have widespread effects later in life for a spectrum of neurological disorders...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2990.2008.01005.x
更新日期:2009-04-01 00:00:00
abstract::Using a combined biochemical and histological approach certain conclusions can be drawn as to the origin of the increase in lysosomal enzymes in white matter from MS brains. Firstly, there is a gradient of lysosomal enzyme activity, plaque greater than periplaque greater than macroscopically normal white matter, which...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1978.tb01357.x
更新日期:1978-11-01 00:00:00
abstract:AIMS:Much evidence demonstrates that Toll-like receptor-4 (TLR4)-mediated microglial activation is an important contributor to the inflammatory injury in intracerebral haemorrhage (ICH). However, the exact mechanism of TLR4-mediated microglial activation induced by ICH is not clear. In addition, microglial autophagy is...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12177
更新日期:2015-06-01 00:00:00
abstract:AIMS:Multiple sclerosis (MS) and neuromyelitis optica (NMO) are inflammatory autoimmune diseases that affect the central nervous system. Several genome-wide and candidate gene studies have identified genetic polymorphisms associated with the risk of MS or NMO. In particular, two recently published studies of meta-analy...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2012.01304.x
更新日期:2013-08-01 00:00:00
abstract::The brain is vulnerable to a number of acute insults, with traumatic brain injury being among the commonest. Neuroinflammation is a common response to acute injury and microglial activation is a key component of the inflammatory response. In the acute and subacute phase it is likely that this response is protective an...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/nan.12006
更新日期:2013-02-01 00:00:00
abstract:AIM:To understand the progression of CLN1 disease and develop effective therapies we need to characterize early sites of pathology. Therefore, we performed a comprehensive evaluation of the nature and timing of early CLN1 disease pathology in the spinal cord, which appears especially vulnerable, and how this may affect...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12658
更新日期:2020-08-25 00:00:00
abstract:AIMS:Amyloid-β (Aβ) oligomers trigger synaptic degeneration that precedes plaque and tangle pathology. However, the signalling molecules that link Aβ oligomers to synaptic pathology remain unclear. Here, we addressed the potential role of RAPGEF2 as a novel signalling molecule in Aβ oligomer-induced synaptic and cognit...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/nan.12686
更新日期:2020-12-20 00:00:00
abstract::An elderly man suffering from dementia associated with hypertension developed right-sided parkinsonism marked by rigidity and flexion. At autopsy the brain showed generalized vascular changes chiefly in the white matter, diffuse plaque and neurofibrillary tangle formation in the temporal cortex, and a discrete gliotic...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1978.tb00548.x
更新日期:1978-07-01 00:00:00
abstract::An unusual inherited progressive distal myopathy of early childhood onset is described in two sisters from a consanguineous Asian family. Motor milestones were normal but gait deteriorated slowly thereafter with development of generalized hypotonia and muscle weakness particularly in the wrist extensors and hand muscl...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1989.tb01145.x
更新日期:1989-01-01 00:00:00
abstract::Telomerase is a ribonucleoprotein enzyme complex that synthesizes telomere DNA. It is detected in 85-90% of malignant tumours in humans, but not in most somatic cells. Because telomerase plays a critical role in cell immortality, it represents an important target for anticancer therapies. We have previously shown that...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2006.00776.x
更新日期:2006-12-01 00:00:00
abstract::Clinical, neuropathological and molecular genetic studies in a 9 month old boy with Pelizaeus-Merzbacher disease are described. The principal clinical features were developmental delay, nystagmus, stridor and seizures. Both brain and spinal cord showed almost complete absence of stainable central myelin, while cranial...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1995.tb01036.x
更新日期:1995-04-01 00:00:00
abstract::Toxicity associated with abnormal protein folding and protein aggregation are major hypotheses for neurodegeneration. This article comparatively reviews the experimental and human tissue-based evidence for the involvement of such mechanisms in neuronal death associated with the motor system disorders of X-linked spino...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1046/j.0305-1846.2003.00518.x
更新日期:2003-12-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by loss of upper and lower motor neurones leading to muscle weakness and paralysis. Despite recent advances in the genetics of ALS, the mechanisms underlying motor neurone degeneration are not fully understood. Mitochondria are know...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2990.2011.01166.x
更新日期:2011-06-01 00:00:00
abstract:AIMS:Transition metals, oxidative stress and neuroinflammation have been proposed as part of a vicious cycle in central nervous system neurodegeneration. Our aim was to study the anti-inflammatory effect of pioglitazone, a peroxisome proliferative activated receptor-γ agonist, on iron-induced oxidative injury in rat br...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2010.01107.x
更新日期:2010-12-01 00:00:00
abstract::Studies in vitro have shown that phosphorylated translation initiation factor 2 alpha (TIF 2 alpha) may have several functions, including regulation of protein synthesis, control of cell death and procurement of resistance to oxidative stress in nerve cells. These properties may have implications in certain human neur...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.2002.t01-1-00410.x
更新日期:2002-12-01 00:00:00
abstract::Dysfunction of the ubiquitin-dependent proteolytic pathway contributes to progressive accumulation of ubiquitinated protein inclusions in neurodegenerative disorders, such as Parkinson's disease (PD). Ubiquitin C-terminal hydrolase-L1 (UCH-L1), alternatively designated protein gene product 9.5 (PGP9.5), is a neural de...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.2001.00313.x
更新日期:2001-04-01 00:00:00
abstract::Transferase dUTP nick-end labelling (TUNEL) analysis was used to compare the occurrence of cell death in the cerebral wall of cocaine-exposed and drug-naïve monkey fetuses. The rhesus monkeys providing the drug-exposed fetuses received 10 mg/kg of cocaine orally (in fruit treats) in the morning and in the evening betw...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.1999.00211.x
更新日期:1999-12-01 00:00:00
abstract::To confirm the intracellular accumulation of amyloid beta-protein (Abeta), we carefully performed immunohistochemistry using brains of cynomolgus monkeys of various ages. Cortical neurones and their large neurites were immunostained with antibodies against Abeta in young monkey brains. In aged monkey brains, intracell...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2004.00624.x
更新日期:2005-04-01 00:00:00
abstract::Protein aggregation, mitochondrial impairment and oxidative stress are common to multiple neurodegenerative diseases. Homeostasis is regulated by a balanced set of anabolic and catabolic responses, which govern removal and repair of damaged proteins and organelles. Macroautophagy is an evolutionarily conserved pathway...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,评审
doi:10.1111/j.1365-2990.2010.01062.x
更新日期:2010-04-01 00:00:00
abstract::In a stereological study of the human substantia nigra (SN), the total number of melanin-positive and melanin-negative neurones from 28 male subjects aged 19-92 years was estimated using a uniform sampling design and optical disectors. There was a significant decrease in the total number of melanin-positive neurones a...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.1365-2990.2002.00393.x
更新日期:2002-08-01 00:00:00
abstract::Two cases are described, one with a multifocal cranial and limb neuropathy of adult onset associated with optic neuropathy, and the other with a diffuse demyelinating neuropathy characterized by congenital cataract, mental retardation and progressive lower limb paresis with an onset in childhood. Extensive investigati...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1046/j.0305-1846.2000.00289.x
更新日期:2000-12-01 00:00:00
abstract:AIM:Recent studies indicate that tau pathology in Alzheimer's disease (AD) does not initially manifest in the cerebral cortex but in selected subcortical nuclei, in particular the locus ceruleus (LC). In this study we correlate both olfactory and brainstem tau pathology with neuritic Braak stages. METHODS:We examined ...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.2011.01244.x
更新日期:2012-10-01 00:00:00
abstract::Patients infected with the malaria parasite Plasmodium falciparum may develop a diffuse reversible encephalopathy, termed cerebral malaria. It is unclear how the intraerythrocytic parasite, which sequesters in the cerebral microvasculature but does not enter the brain parenchyma, induces this neurological syndrome. Ad...
journal_title:Neuropathology and applied neurobiology
pub_type: 临床试验,杂志文章
doi:10.1046/j.1365-2990.1999.00188.x
更新日期:1999-08-01 00:00:00
abstract:OBJECTIVE:To perform a systematic review and meta-analysis on the prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults. METHODS:We systematically reviewed and performed a meta-analysis on the prevalence of TDP-43 proteinopathy in older adults with normal c...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章,meta分析
doi:10.1111/nan.12430
更新日期:2018-04-01 00:00:00
abstract::Transparent Golgi preparations counterstained for Alzheimer's neurofibrillary changes rendered possible the demonstration of neuropil threads in defined cellular processes. Only dendrites of tangle-bearing cortical nerve cells were found to contain neuropil threads. Processes of glial cells as well as axons present in...
journal_title:Neuropathology and applied neurobiology
pub_type: 杂志文章
doi:10.1111/j.1365-2990.1988.tb00864.x
更新日期:1988-01-01 00:00:00