Abstract:
BACKGROUND:The molecular mechanisms underlying Alzheimer's disease (AD) are yet to be fully elucidated. The so-called "amyloid cascade hypothesis" has long been the prevailing paradigm for causation of disease, and is today being revisited in relation to other pathogenic pathways, such as oxidative stress, neuroinflammation and energy dysmetabolism. The peroxisome proliferator-activated receptors (PPARs) are expressed in the central nervous system (CNS) and regulate many physiological processes, such as energy metabolism, neurotransmission, redox homeostasis, autophagy and cell cycle. Among the three isotypes (α, β/δ, γ), PPARγ role is the most extensively studied, while information on α and β/δ are still scanty. However, recent in vitro and in vivo evidence point to PPARα as a promising therapeutic target in AD. CONCLUSION:This review provides an update on this topic, focussing on the effects of natural or synthetic agonists in modulating pathogenetic mechanisms at AD onset and during its progression. Ligandactivated PPARα inihibits amyloidogenic pathway, Tau hyperphosphorylation and neuroinflammation. Concomitantly, the receptor elicits an enzymatic antioxidant response to oxidative stress, ameliorates glucose and lipid dysmetabolism, and stimulates autophagy.
journal_name
Curr Alzheimer Resjournal_title
Current Alzheimer researchauthors
D'Orio B,Fracassi A,Ceru MP,Moreno Sdoi
10.2174/1567205014666170505094549subject
Has Abstractpub_date
2018-02-22 00:00:00pages
345-354issue
4eissn
1567-2050issn
1875-5828pii
CAR-EPUB-83292journal_volume
15pub_type
杂志文章,评审abstract:BACKGROUND:Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that eventually leads to severe cognitive impairment. Although the exact etiologies of AD still remain elusive, increasing evidence suggests that neuroinflammation cascades mediated by microglial cells are associated with AD. Piper sarme...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205016666190228124630
更新日期:2019-01-01 00:00:00
abstract::At present, the search for preventive strategies for cognitive decline and dementia appears to be of crucial importance, given that the therapeutic options currently available have demonstrated limited efficacy. Cumulative epidemiological evidence suggested that vascular and vascular-related factors may be important f...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720511796391818
更新日期:2011-08-01 00:00:00
abstract::The serine hydrolase butyrylcholinesterase (BChE), like the related enzyme acetylcholinesterase (AChE), co-regulates metabolism of the neurotransmitter acetylcholine. In the human brain BChE is mainly expressed in white matter and glia and in distinct populations of neurons in regions that are important in cognition a...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205013666160404120542
更新日期:2016-01-01 00:00:00
abstract::CATIE-AD was a multicenter effectiveness trial of atypical antipsychotics in patients with agitation and psychosis associated with AD who resided in the community. The study enrolled 421 participants. In this paper we present and discuss baseline characteristics of participants (demographics, cognitive, behavioral, an...
journal_title:Current Alzheimer research
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2174/156720507781077214
更新日期:2007-07-01 00:00:00
abstract:BACKGROUND/OBJECTIVES:Increasing evidence suggests the importance of neuroinflammation in the pathogenesis of Alzheimer's disease (AD), which is a complex neurodegenerative disorder. Complement activation occurs in the brain of patients with AD and seems to contribute to an important local inflammatory state. Increased...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205013666161013091934
更新日期:2017-01-01 00:00:00
abstract:OBJECTIVE:To carry out meaningful comparisons on results of different research studies on mild cognitive impairment (MCI), it is critical to select an appropriate objective memory test to examine memory deficit. We aim to refine the operational criteria of amnestic MCI (aMCI) on neuropsychological tests that optimally ...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205012666150530202729
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:There is a growing body of pre-clinical evidence suggesting that lithium (Li) may protect neurons from a range of neurotoxic insults, hence the term neuroprotective effects. Does Li have similar effects also in human subjects? METHODS:We reviewed the neuroimaging literature investigating the association bet...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205013666160219112712
更新日期:2016-01-01 00:00:00
abstract::The occurrence of a plaque-dependent inflammation in Alzheimer's disease has been extensively documented in both human specimens and transgenic models of the disease. Since insoluble plaques are present in AD patients from early preclinical stages of the pathology, the point at which neuroinflammation first occurs in ...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720511795255982
更新日期:2011-03-01 00:00:00
abstract::Alzheimer's disease is a neurodegenerative disorder characterized by amyloid deposits and neurofibrillary tangles. Cholinergic dysfunction is also a main pathological feature of the disease. Nevertheless, the links between cholinergic dysfunction and neuropathological hallmarks of Alzheimer's are still unknown. In the...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720509787602843
更新日期:2009-04-01 00:00:00
abstract::Mild cognitive impairment (MCI) is a nosological entity associated with a higher risk of developing dementia. Previous evidence indicates that behavioral and psychological symptoms of dementia (BPSDs) frequently occur in individuals of MCI. These neuropsychiatric manifestations may predict conversion to dementia. Howe...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205013666160502123129
更新日期:2016-01-01 00:00:00
abstract::This article presents a new paradigm of Artificial Neural Networks (ANNs): the Auto-Contractive Maps (Auto-CM). The Auto-CM differ from the traditional ANNs under many viewpoints: the Auto-CM start their learning task without a random initialization of their weights, they meet their convergence criterion when all thei...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720508785908928
更新日期:2008-10-01 00:00:00
abstract::The marginal division (MrD) is a neostriatum subregion that links the limbic system and basal nucleus of Meynert; it is an important subcortical center that is involved in learning and memory. Alzheimer's disease (AD) is a neurodegenerative disorder and the most common cause of dementia in the elderly. AD clinically m...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205011666140110112608
更新日期:2014-02-01 00:00:00
abstract:BACKGROUND:The USA National Task Group (NTG) guidelines advocate the use of an adapted version of Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) for dementia screening of individuals with Down syndrome (DS) and with other forms of ID (non-DS). OBJECTIVE:In order to meet these ...
journal_title:Current Alzheimer research
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2174/1567205014666170117094757
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Vascular disease is associated with increased risk of dementia. Vascular health worsens with age. We investigated the relationship between self-reported vascular disease and brain pathology. METHODS:Brain donations to the population-based MRC Cognitive Function and Ageing Study (n=456, age range 66-103 year...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720512801322654
更新日期:2012-07-01 00:00:00
abstract::Rodents housed in an enriched environment, exercise by running or perform learning and memory tasks show an increase in hippocampal neurogenesis. We show that both environmental enrichment, as well as performance in the Morris water maze, a hippocampal-dependent learning task, leads to an increase in local VEGF expres...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720506775697133
更新日期:2006-02-01 00:00:00
abstract::Parkinson disease (PD) is the second most prevalent neurodegenerative disorder after Alzheimer's disease (AD). The formation of the cytoplasmic inclusions named "Lewy bodies" in the brain, considered to be a marker for neuronal degeneration in PD and dementia with Lewy bodies. However, Lewy bodies (LBs) are also obser...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205011310060002
更新日期:2013-07-01 00:00:00
abstract::Alzheimer's disease (AD) is currently the most prominent form of dementia among the elderly. Although AD manifests in late adult life, it is not clear when the disease actually starts and how long the neuropathological processes take to develop AD. The major unresolved question is the timing and the nature of triggeri...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720507780362164
更新日期:2007-04-01 00:00:00
abstract::Despite the known validity of clinical diagnostic criteria, significant overlap of clinical symptoms between Frontotemporal dementia (FTD) subtypes exists in several cases, resulting in great uncertainty of the diagnostic boundaries. We evaluated the perfusion between FTD subtypes using brain perfusion (99m)Tc-HMPAO S...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205011666141107125104
更新日期:2014-01-01 00:00:00
abstract::The aggregation of the microtubule-associated protein tau into paired-helical filaments is the defining characteristic of the tauopathies. It has become apparent that the hyperphosphorylation of tau likely plays a role in the aggregation process and thus strategies to reduce tau phosphorylation are generating wide int...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720509789207967
更新日期:2009-10-01 00:00:00
abstract:OBJECTIVES:REM sleep behavior disorder (RBD), with its main clinical symptoms of nightmares with dream-enacting behavior, is considered as a possible precursor of neurodegenerative disease. Obstructive Sleep Apnea Syndrome (OSAS) is known to be capable of provoking RBD-like symptoms by apneic event related arousals. Th...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205014666170523094938
更新日期:2017-01-01 00:00:00
abstract:BACKGROUND:Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular amyloid plaque and neurofibrillary tangles in the brain. Studies have shown that neurons are able to re-enter the cell cycle, but not enough to enable full replication. This leads to cell death and consequent neurodegener...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205014666170713160407
更新日期:2018-01-01 00:00:00
abstract::Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the fourth leading cause of death in the United States and most common cause of adult-onset dementia. The major hallmarks of AD are the formation of senile amyloid plaques made of beta amyloid and neurofibrillary tangles (NFT) which are primarily...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/156720501209151019105647
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Alzheimer's disease (AD) is a neurodegenerative disease featured by memory loss, neuroinflammation and oxidative stress. Overproduction or insufficient clearance of Aβ leads to its pathological aggregation and deposition, which is considered the predominant neuropathological hallmark of AD. Therefore, reduci...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205015666180404160625
更新日期:2018-01-01 00:00:00
abstract::Evidence from basic molecular biology has noted a critical role of GSK-3 in Alzheimer's disease (AD) pathogenesis such as beta-amyloid (Aβ) production and accumulation, the formation of neurofibrillary tangle (NFT), and neuronal degeneration. Aβ generation and deposition represents a key feature and is generated from ...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720512802455386
更新日期:2012-09-01 00:00:00
abstract::At present, the etiology of Alzheimer's disease (AD) is still unclear, but both genetic and non-genetic factors are thought to take part in the etiopathogenesis of AD. Epidemiologic researches revealed that genetic factors played a decisive role in the development of both early-onset AD (EOAD) and late-onset AD (LOAD)...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/15672050113109990155
更新日期:2013-10-01 00:00:00
abstract::The remarkable potentiality of bone marrow-derived mesenchymal stem cells (BM-MSCs) after transplantation to models of neurological disease and injury has been described. We have previously published data confirming the influence of BM-MSCs on β-amyloid (Aβ) deposition in an Alzheimer's disease (AD) mouse model. Howev...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:
更新日期:2013-06-01 00:00:00
abstract:BACKGROUND:Cholinesterase inhibitors are the first line of therapy for the management of Alzheimer's disease (AD), however, it is now established that they provide only temporary and symptomatic relief, besides, having several inherited side-effects. Therefore, an alternative drug discovery method is used to identify n...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205016666181212155147
更新日期:2019-01-01 00:00:00
abstract::According to the current paradigm, the main cause of AD is the accumulation of neurotoxic amyloid beta (Aβ) peptide aggregates resulting from the cleavage of the amyloid precursor protein into peptides of different length, with the 42 amino acid long Aβ42 being the most toxic form. Aβ can aggregate and form plaques in...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/1567205013666160222112444
更新日期:2016-01-01 00:00:00
abstract::The increasing prevalence of obesity world-wide has an expected consequent increase in diabetes and cardiovascular disease. Less attention has been paid to the effect of obesity on dementia. This overview discusses methodological issues related to the epidemiologic study of obesity and dementia, reviews results of lon...
journal_title:Current Alzheimer research
pub_type: 杂志文章,评审
doi:10.2174/156720507780362074
更新日期:2007-04-01 00:00:00
abstract::Differential diagnosis of AD is still a challenge due to overlapping features with other types of dementia. Biomarkers for the differential diagnosis of AD can improve the diagnostic value of the disease and ensure an appropriate treatment of patients. The aim of this study was to evaluate the potential of two neo-epi...
journal_title:Current Alzheimer research
pub_type: 杂志文章
doi:10.2174/1567205012666150710111211
更新日期:2015-01-01 00:00:00