Abstract:
:Over the past two decades there have been significant advances in our understanding of copper homeostasis and the pathological consequences of copper dysregulation. Cumulative evidence is revealing a complex regulatory network of proteins and pathways that maintain copper homeostasis. The recognition of copper dysregulation as a key pathological feature in prominent neurodegenerative disorders such as Alzheimer's, Parkinson's, and prion diseases has led to increased research focus on the mechanisms controlling copper homeostasis in the brain. The copper-transporting P-type ATPases (copper-ATPases), ATP7A and ATP7B, are critical components of the copper regulatory network. Our understanding of the biochemistry and cell biology of these complex proteins has grown significantly since their discovery in 1993. They are large polytopic transmembrane proteins with six copper-binding motifs within the cytoplasmic N-terminal domain, eight transmembrane domains, and highly conserved catalytic domains. These proteins catalyze ATP-dependent copper transport across cell membranes for the metallation of many essential cuproenzymes, as well as for the removal of excess cellular copper to prevent copper toxicity. A key functional aspect of these copper transporters is their copper-responsive trafficking between the trans-Golgi network and the cell periphery. ATP7A- and ATP7B-deficiency, due to genetic mutation, underlie the inherited copper transport disorders, Menkes and Wilson diseases, respectively. Their importance in maintaining brain copper homeostasis is underscored by the severe neuropathological deficits in these disorders. Herein we will review and update our current knowledge of these copper transporters in the brain and the central nervous system, their distribution and regulation, their role in normal brain copper homeostasis, and how their absence or dysfunction contributes to disturbances in copper homeostasis and neurodegeneration.
journal_name
Front Aging Neuroscijournal_title
Frontiers in aging neuroscienceauthors
Telianidis J,Hung YH,Materia S,Fontaine SLdoi
10.3389/fnagi.2013.00044subject
Has Abstractpub_date
2013-08-23 00:00:00pages
44issn
1663-4365journal_volume
5pub_type
杂志文章abstract::Abnormal cerebral blood flow (CBF) and resting-state functional connectivity (rs-FC) are sensitive biomarkers of disease progression and prognosis. This study investigated neural underpinnings of motor and cognitive recovery by longitudinally studying the changes of CBF and FC in pontine infarction (PI). Twenty patien...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2020.577899
更新日期:2020-11-19 00:00:00
abstract::Exercise may be the most commonly offered yet least consistently followed therapeutic advice for people with Parkinson's disease (PD). Epidemiological studies of prospectively followed cohorts have shown a lower risk for later developing PD in healthy people who report moderate to high levels of physical activity, and...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnagi.2020.00186
更新日期:2020-06-19 00:00:00
abstract::Ishigami and Klein (2010) showed that scores of the three attention networks (alerting, orienting, and executive control) measured with the two versions of the Attention Network Test (ANT; Fan et al., 2002; Callejas et al., 2005) were robust over 10 sessions of repeated testing even though practice effects were consis...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2011.00017
更新日期:2011-11-15 00:00:00
abstract:Background:Studying structural brain aging is important to understand age-related pathologies, as well as to identify the early manifestations of the Alzheimer's disease (AD) continuum. In this study, we investigated the long-term trajectory of physiological and pathological brain aging in a large number of participant...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2019.00147
更新日期:2019-06-18 00:00:00
abstract::Similar to humans, the normal aged rat population is not homogeneous in terms of cognitive function. Two distinct subpopulations of aged Sprague-Dawley rats can be identified on the basis of spatial memory performance in the hole-board paradigm. It was the aim of the study to reveal protein changes relevant to aging a...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2019.00198
更新日期:2019-07-31 00:00:00
abstract::With promising results in recent treatment trials for Alzheimer's disease (AD), it becomes increasingly important to distinguish AD at early stages from other causes for cognitive impairment. However, existing diagnostic methods are either invasive (lumbar punctures, PET) or inaccurate Magnetic Resonance Imaging (MRI)...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2017.00114
更新日期:2017-04-25 00:00:00
abstract::[This corrects the article DOI: 10.3389/fnagi.2019.00343.]. ...
journal_title:Frontiers in aging neuroscience
pub_type: 已发布勘误
doi:10.3389/fnagi.2020.00030
更新日期:2020-02-18 00:00:00
abstract:BACKGROUND:Platelet Rich Plasma (PRP) has shown positive and long-lasting effects in patients with tendinopathies. However, information about age-related differences in the clinical outcome is limited. Aim of this retrospective study was to compare the efficacy of PRP therapy in young and elderly subjects suffering for...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2015.00228
更新日期:2015-12-10 00:00:00
abstract::Background: Gray matter (GM) alterations in Parkinson's disease (PD) patients with rapid eye movement sleep behavior disorder (RBD) have been demonstrated in many neuroimaging studies using voxel-based morphometry (VBM). However, the inconsistent findings between studies cannot be applied to clinical practice as a neu...
journal_title:Frontiers in aging neuroscience
pub_type:
doi:10.3389/fnagi.2020.00213
更新日期:2020-08-12 00:00:00
abstract::Patients with diabetes suffer the higher risk of dementia and the underlying pathological mechanism of cognitive dysfunction in diabetes is not fully understood. In this study, we explore whether the cognitive impairment in the diabetic rat is associated with increased blood brain barrier (BBB) permeability and the ch...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2018.00129
更新日期:2018-05-07 00:00:00
abstract::Astrocytes are the most abundant cells of the central nervous system; they have a predominant role in maintaining brain metabolism. In this sense, abnormal metabolic states have been found in different neuropathological diseases. Determination of metabolic states of astrocytes is difficult to model using current exper...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2017.00023
更新日期:2017-02-13 00:00:00
abstract:Background:Age-related cognitive decline begins in middle age and persists with age. Leukocyte telomere length (LTL) decreases with age and is enhanced by inflammation and oxidative stress. However, whether shorter LTL correlates with cognitive decline remains controversial. Aims:We aimed to investigate the relationsh...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2020.527658
更新日期:2020-10-30 00:00:00
abstract::Background: Two main models have been advanced to explain the asymmetries observed in the representation and processing of emotions. The first model, labeled "the right hemisphere hypothesis," assumes a general dominance of the right hemisphere for all emotions, regardless of affective valence. The second model, named...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnagi.2019.00055
更新日期:2019-03-19 00:00:00
abstract::There is growing consensus that intervention and treatment of Huntington disease (HD) should occur at the earliest stage possible. Various early-intervention methods for this fatal neurodegenerative disease have been identified, but preventive clinical trials for HD are limited by a lack of knowledge of the natural hi...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2014.00078
更新日期:2014-04-22 00:00:00
abstract::Alzheimer's disease (AD) is associated with cognitive and non-cognitive symptoms for which there are currently no effective therapies. We have previously reported that cotinine, a natural product obtained from tobacco leaves, prevented memory loss and diminished amyloid-β (Aβ) plaque pathology in transgenic 6799 mice ...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2014.00162
更新日期:2014-07-23 00:00:00
abstract::Objectives: Postural control in elderly people is impaired by degradations of sensory, motor, and higher-level adaptive mechanisms. Here, we characterize the effects of a progressive balance training program on these postural control impairments using a brain network model based on system identification techniques. Me...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2017.00273
更新日期:2017-08-11 00:00:00
abstract::Aggregated tau is a hallmark neuropathological feature in numerous neurodegenerative disorders. Previous studies aiming to validate aggregated tau pathology as a pathogenic driver of neurodegeneration in correlation to characteristic behavioral phenotypes have had shortcomings. Although studies on soluble tau patholog...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2020.537712
更新日期:2020-11-05 00:00:00
abstract::Ageing disorders can be defined as the progressive and cumulative outcome of several defective cellular mechanisms as well as metabolic pathways, consequently resulting in degeneration. Environment plays an important role in its pathogenesis. In contrast, developmental disorders arise from inherited mutations and usua...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnagi.2014.00151
更新日期:2014-07-10 00:00:00
abstract::Manganese (Mn) is an essential metal and has important physiological functions for human health. However, exposure to excess levels of Mn in occupational settings or from environmental sources has been associated with a neurological syndrome comprising cognitive deficits, neuropsychological abnormalities and parkinson...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2013.00023
更新日期:2013-06-24 00:00:00
abstract::Studies of the neural mechanisms of navigation and context discrimination have generated a powerful heuristic for understanding how neural codes, circuits, and computations contribute to accurate behavior as animals traverse and learn about spatially extended environments. It is assumed that memories are updated as a ...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2012.00022
更新日期:2012-08-08 00:00:00
abstract::Background: Facial emotion recognition (FER) is impaired in individuals with frontotemporal dementia (FTD) and Alzheimer's disease (AD) when compared to healthy older adults. Since deficits in emotion recognition are closely related to caregiver burden or social interactions, researchers have fundamental interest in F...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2017.00389
更新日期:2017-11-30 00:00:00
abstract::Background and Purpose: Olfactory dysfunction (OD) is a common non-motor symptom of Parkinson disease (PD). However, the relationship between OD and neuropathologic proteins in cerebrospinal fluid (CSF) from PD patients remains unclear. Methods: 166 PD patients were included in the study. Overall olfactory function wa...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2020.594324
更新日期:2020-12-11 00:00:00
abstract::The recent advent of tau-specific positron emission tomography (PET) has enabled in vivo assessment of tau pathology in Alzheimer's disease (AD). However, because PET scanners have limited spatial resolution, the measured signals of small brain structures or atrophied areas are underestimated by partial volume effects...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2018.00223
更新日期:2018-07-18 00:00:00
abstract::Postoperative cognitive dysfunction (POCD) is a significant complication of surgery, particularly in elderly patients. Emerging researches showed that long non-coding RNA (lncRNA) may play a vital role in the pathogenesis of POCD. Here we aimed to identify potential key lncRNAs involved in the development of POCD. Lnc...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2019.00181
更新日期:2019-07-17 00:00:00
abstract::The semantic verbal fluency task is broadly used in the neuropsychological assessment of elderly subjects. Even some studies have identified differences in verbal fluency clustering and switching measures between subjects with normal aging and a clinical condition such as mild cognitive impairment (MCI) and Alzheimer'...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2014.00141
更新日期:2014-07-01 00:00:00
abstract::The dorsal raphe nucleus (DRN) has been repeatedly implicated as having a significant relationship with depression, along with its serotoninergic innervation. However, functional connectivity of the DRN in depression is not well understood. The current study aimed to isolate functional connectivity of the DRN distinct...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2017.00236
更新日期:2017-08-02 00:00:00
abstract::Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the ...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2014.00185
更新日期:2014-07-29 00:00:00
abstract:BACKGROUND:The cognitive status is generally considered as a major determinant of rehabilitation outcome in Parkinson's disease (PD). No studies about the effect of cognitive impairment on motor rehabilitation outcomes in PD have been performed before. OBJECTIVE:This study is aimed to evaluate the impact of cognitive ...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2016.00192
更新日期:2016-08-11 00:00:00
abstract::Disrupted metal homeostasis is a consistent feature of neurodegenerative disease in humans and is recapitulated in mouse models of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS) and neuronal ceriod lipofuscinosis. While the definitive pathogenesis of neurodegenerative disease in humans r...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2014.00015
更新日期:2014-02-11 00:00:00
abstract::Neurofilament light (NFL) is a putative biomarker of neurodegeneration. This study evaluates the correlative association of NFL with Alzheimer's disease (AD) indices. Relevant studies were identified after a literature search in electronic databases and study selection was based on pre-determined eligibility criteria....
journal_title:Frontiers in aging neuroscience
pub_type:
doi:10.3389/fnagi.2019.00254
更新日期:2019-09-13 00:00:00