scholarly journals Hypoxia and the Kynurenine Pathway: Implications and Therapeutic Prospects in Alzheimer’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Oluyomi Stephen Adeyemi ◽  
Oluwakemi Josephine Awakan ◽  
Lawrence Boluwatife Afolabi ◽  
Damilare Emmanuel Rotimi ◽  
Elizabeth Oluwayemi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protective Factor ◽  
Hypoxia Inducible Factor ◽  
Kynurenine Pathway ◽  
Dual Function ◽  
New Therapeutic Approaches ◽  
Molecular Events ◽  
Pathway Activation ◽  
Organ Tissue

Neurodegenerative diseases (NDs) like Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson’s disease, and Huntington’s disease predominantly pose a significant socioeconomic burden. Characterized by progressive neural dysfunction coupled with motor or intellectual impairment, the pathogenesis of ND may result from contributions of certain environmental and molecular factors. One such condition is hypoxia, characterized by reduced organ/tissue exposure to oxygen. Reduced oxygen supply often occurs during the pathogenesis of ND and the aging process. Despite the well-established relationship between these two conditions (i.e., hypoxia and ND), the underlying molecular events or mechanisms connecting hypoxia to ND remain ill-defined. However, the relatedness may stem from the protective or deleterious effects of the transcription factor, hypoxia-inducible factor 1-alpha (HIF-1α). The upregulation of HIF-1α occurs in the pathogenesis of most NDs. The dual function of HIF-1α in acting as a “killer factor” or a “protective factor” depends on the prevailing local cellular condition. The kynurenine pathway is a metabolic pathway involved in the oxidative breakdown of tryptophan. It is essential in neurotransmission and immune function and, like hypoxia, associated with ND. Thus, a good understanding of factors, including hypoxia (i.e., the biochemical implication of HIF-1α) and kynurenine pathway activation in NDs, focusing on Alzheimer’s disease could prove beneficial to new therapeutic approaches for this disease, thus the aim of this review.

Associations Between Obesity and Alzheimer’s Disease: Multiple Bioinformatic Analyses

2021 ◽  
pp. 1-11
Author(s):  
Qi-Shuai Zhuang ◽  
Lei Meng ◽  
Zhe Wang ◽  
Liang Shen ◽  
Hong-Fang Ji
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Network Analysis ◽  
Drug Targets ◽  
Protective Factor ◽  
Genetic Locus ◽  
Meta Analysis ◽  
Current Evidence ◽  
Causal Association ◽  
Ppi Network

Background: Identifying modifiable risk factors, such as obesity, to lower the prevalence of Alzheimer’s disease (AD) has gained much interest. However, whether the association is causal remains to be evaluated. Objective: The present study was designed: 1) to make a quantitative assessment of the association between obesity and AD; 2) to validate whether there was a causal association between them; and 3) to provide genetic clues for the association through a network-based analysis. Methods: Two-sample Mendelian randomization (2SMR) analysis, meta-analysis, and protein-protein interaction (PPI) network analysis, were employed. Results: Firstly, the meta-analysis based on 9 studies comprising 6,986,436 subjects indicated that midlife obesity had 33%higher AD odds than controls (OR = 1.33, 95%CI = [1.03, 1.62]), while late-life obesity were inversely associated with AD risk (OR = 0.57, 95%CI = [0.47, 0.68]). Secondly, 2SMR analysis indicated that there was no causal association between them. Thirdly, CARTPT was identified to be shared by the anti-obesity drug targets and AD susceptibility genes. Further PPI network analysis found that CARTPT interacted with CD33, a strong genetic locus linked to AD. Finally, 2SMR analysis showed that CNR1 could be a protective factor for AD. Conclusion: Multiple bioinformatic analyses indicated that midlife obesity might increase the risk of AD, while current evidence indicated that there was no causal association between them. Further, CARTPT might be an important factor linking the two disease conditions. It could help to better understand the mechanisms underlying the associations between obesity and AD.

The cyclooxygenase 2 -765 C promoter allele is a protective factor for Alzheimer's disease

2006 ◽  
Vol 395 (3) ◽  
pp. 240-243 ◽  
Author(s):  
Laila Abdullah ◽  
Ghania Ait-Ghezala ◽  
Fiona Crawford ◽  
Timothy A. Crowell ◽  
Warren W. Barker ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protective Factor ◽  
Cyclooxygenase 2 ◽  
Promoter Allele

scholarly journals Trait mindfulness is associated with less amyloid, tau, and cognitive decline in individuals at risk for Alzheimer's disease

2021 ◽  
Author(s):  
Cherie Strikwerda-Brown ◽  
Hazal Ozlen ◽  
Alexa Pichet Binette ◽  
Marianne Chapleau ◽  
Natalie Marchant ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
At Risk ◽  
Cognitive Decline ◽  
Protective Factor ◽  
Present Moment ◽  
Trait Mindfulness ◽  
Cognitive Assessments ◽  
Positron Emission

Mindfulness, defined as the ability to engage in non-judgmental awareness of the present moment, has been associated with an array of health benefits. Mindfulness may also represent a protective factor for Alzheimer's disease (AD). Here, we tested the potential protective effect of trait mindfulness on cognitive decline and AD pathology in older adults at risk of AD dementia. Measures of trait mindfulness, longitudinal cognitive assessments, and AB- and tau- positron emission tomography (PET) scans were collected in 261 nondemented older adults with a family history of AD dementia from the PREVENT-AD observational cohort study. Multivariate partial least squares analyses were used to examine relationships between combinations of different facets of trait mindfulness and (1) cognitive decline, (2) AB, and (3) tau. Higher levels of trait mindfulness, particularly mindful nonjudgment, were associated with less cognitive decline, AB, and tau. Trait mindfulness may represent a psychological protective factor for AD dementia.

scholarly journals Beyond Alzheimer's disease: Can bilingualism be a more generalized protective factor in neurodegeneration?

2020 ◽  
Vol 147 ◽  
pp. 107593
Author(s):  
Toms Voits ◽  
Christos Pliatsikas ◽  
Holly Robson ◽  
Jason Rothman
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protective Factor

scholarly journals Estrogen Therapy Fails to Alter Amyloid Deposition in the PDAPP Model of Alzheimer’s Disease

Endocrinology ◽  
2005 ◽  
Vol 146 (6) ◽  
pp. 2774-2781 ◽  
Author(s):  
Pattie S. Green ◽  
Kelly Bales ◽  
Steven Paul ◽  
Guojun Bu
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protective Factor ◽  
Estrogen Therapy ◽  
Epidemiological Studies ◽  
Estrogen Replacement ◽  
Estrogen Deprivation ◽  
Model Of Alzheimer’S Disease ◽  
Plasma Estradiol ◽  
Vaginal Cytology

Abstract Epidemiological studies implicate estrogen deprivation as a risk factor for Alzheimer’s disease and postmenopausal estrogen replacement as protective factor. One potential mechanism involves estrogen attenuation of β-amyloid (Aβ) peptide accumulation. We examined the effect of estrogen on amyloid accumulation in female PDAPP mice, which express human amyloid precursor protein (APP) with the V717F mutation. These animals deposit Aβ 1–42 in the hippocampus and neocortex and develop Alzheimer-like neuropathology. Mice were subjected to ovariectomy, ovariectomy with estrogen replacement, or sham surgery at 3 months of age, and levels of cerebral Aβ 1–40 and 1–42 were determined after 5 months of treatment. Neither estrogen deprivation nor estrogen replacement altered Aβ accumulation in the hippocampus or neocortex. Similarly, immunoreactivity for full-length human APP and secreted APPα was unchanged. Estrogen status of the animals was confirmed using a variety of techniques, including uterine and pituitary weight, vaginal cytology, and plasma estradiol concentrations. There was no correlation between plasma estradiol levels and accumulation of either Aβ 1–40 or Aβ 1–42 in the brain. Our observations indicate that long-term estrogen therapy does not alter amyloid pathology in PDAPP mice, an animal model of Alzheimer’s disease, and question the role of estrogen in Aβ deposition in brain.

scholarly journals Hydroxypyridinone-Diamine Hybrids as Potential Neuroprotective Agents in the PC12 Cell-Line Model of Alzheimer's Disease

2019 ◽  
Vol 12 (4) ◽  
pp. 162
Author(s):  
Lohou ◽  
Sasaki ◽  
Boullier ◽  
Duplantier ◽  
Sonnet
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Advanced Glycation Endproducts ◽  
Carbonyl Stress ◽  
Glycation Endproducts ◽  
New Therapeutic Approaches ◽  
Reactive Carbonyl Species ◽  
Model Of Alzheimer’S Disease ◽  
Induced Apoptosis

There is an urgent need to propose effective treatments for Alzheimer’s disease (AD). Although the origin of the disease is poorly understood, several therapeutic options have been proposed. The new therapeutic approaches targeting biometal-mediated neurodegenerative pathways appear to be interesting ones. As a continuation of our preceding studies, two novel series of advanced glycation endproducts (AGE)/advanced lipid peroxidation endproducts (ALE) inhibitors have been developed as multifunctional scavengers. This extended work allowed us to highlight the new hydroxypyridinone-diamine hybrid IIa-3 bearing a C4 alkyl linker between the two pharmacophores. This derivative exhibited preserved potent capacities to trap reactive carbonyl species (vicinal diamine function) as well as reactive oxygen species and transition metals (hydroxypyridinone moiety) in comparison with previously described lead compound 1. In addition, its good predicted absorption, distribution, metabolism and excretion (ADME) properties were correlated with a better efficacy to inhibit in vitro methylglyoxal-induced apoptosis in neuronal-like PC12 cells. This new promising agent revealed improved druglikeness and ability to prevent biometal-mediated oxidative and carbonyl stress amplification involved in AD pathogenesis.

scholarly journals Pleiotropic Protective Effects of Phytochemicals in Alzheimer's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Sergio Davinelli ◽  
Nadia Sapere ◽  
Davide Zella ◽  
Renata Bracale ◽  
Mariano Intrieri ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Disorder ◽  
Protective Effects ◽  
Drug Candidates ◽  
Molecular Events ◽  
Therapeutic Value ◽  
Phytochemical Compounds ◽  
Multiple Levels ◽  
The Brain

Alzheimer’s disease (AD) is a severe chronic neurodegenerative disorder of the brain characterised by progressive impairment in memory and cognition. In the past years an intense research has aimed at dissecting the molecular events of AD. However, there is not an exhaustive knowledge about AD pathogenesis and a limited number of therapeutic options are available to treat this neurodegenerative disease. Consequently, considering the heterogeneity of AD, therapeutic agents acting on multiple levels of the pathology are needed. Recent findings suggest that phytochemicals compounds with neuroprotective features may be an important resources in the discovery of drug candidates against AD. In this paper we will describe some polyphenols and we will discuss their potential role as neuroprotective agents. Specifically, curcumin, catechins, and resveratrol beyond their antioxidant activity are also involved in antiamyloidogenic and anti-inflammatory mechanisms. We will focus on specific molecular targets of these selected phytochemical compounds highlighting the correlations between their neuroprotective functions and their potential therapeutic value in AD.

NEUROINFLAMMATION, DEPRESSION AND ALZHEIMER’S DISEASE: INSIGHTS FROM THE KYNURENINE PATHWAY

2017 ◽  
Vol 13 (7) ◽  
pp. P181-P182
Author(s):  
Auriel A. Willette ◽  
Joseph L. Webb ◽  
Robert Dantzer
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Kynurenine Pathway
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