scholarly journals Corticotropin-Releasing Factor (CRF), CRF-Binding Protein (CRF-BP), and CRF/CRF-BP Complex in Alzheimer's Disease and Control Postmortem Human Brain

2002 ◽  
Vol 68 (5) ◽  
pp. 2053-2060 ◽  
Author(s):  
Dominic P. Behan ◽  
On Khongsaly ◽  
Michael J. Owens ◽  
Hyung D. Chung ◽  
Charles B. Nemeroff ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Binding Protein ◽  
Corticotropin Releasing Factor ◽  
Postmortem Human Brain ◽  
And Control

Phenylalanine Metabolism is Dysregulated in Human Hippocampus with Alzheimer’s Disease Related Pathological Changes

2021 ◽  
pp. 1-14
Author(s):  
Pan Liu ◽  
Qian Yang ◽  
Ning Yu ◽  
Yan Cao ◽  
Xue Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Pathological Examination ◽  
Pathological Changes ◽  
Targeted Metabolomics ◽  
Phenylpyruvic Acid ◽  
Postmortem Human Brain ◽  
Metabolic Dysregulation ◽  
Phenylalanine Metabolism

Background: Alzheimer’s disease (AD) is one of the most challenging diseases causing an increasing burden worldwide. Although the neuropathologic diagnosis of AD has been established for many years, the metabolic changes in neuropathologic diagnosed AD samples have not been fully investigated. Objective: To elucidate the potential metabolism dysregulation in the postmortem human brain samples assessed by AD related pathological examination. Methods: We performed untargeted and targeted metabolomics in 44 postmortem human brain tissues. The metabolic differences in the hippocampus between AD group and control (NC) group were compared. Results: The results show that a pervasive metabolic dysregulation including phenylalanine metabolism, valine, leucine, and isoleucine biosynthesis, biotin metabolism, and purine metabolism are associated with AD pathology. Targeted metabolomics reveal that phenylalanine, phenylpyruvic acid, and N-acetyl-L-phenylalanine are upregulated in AD samples. In addition, the enzyme IL-4I1 catalyzing transformation from phenylalanine to phenylpyruvic acid is also upregulated in AD samples. Conclusion: There is a pervasive metabolic dysregulation in hippocampus with AD-related pathological changes. Our study suggests that the dysregulation of phenylalanine metabolism in hippocampus may be an important pathogenesis for AD pathology formation.

scholarly journals Corticotropin releasing factor-binding protein (CRF-BP) as a potential new therapeutic target in Alzheimer’s disease and stress disorders

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Dorien Vandael ◽  
Natalia V. Gounko
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neurodegenerative Diseases ◽  
Therapeutic Target ◽  
Life Stress ◽  
Binding Protein ◽  
Critical Role ◽  
Treatment Strategies ◽  
Corticotropin Releasing Factor ◽  
Stress Disorders

Abstract Alzheimer’s disease is the most common cause of dementia and one of the most complex human neurodegenerative diseases. Numerous studies have demonstrated a critical role of the environment in the pathogenesis and pathophysiology of the disease, where daily life stress plays an important role. A lot of epigenetic studies have led to the conclusion that chronic stress and stress-related disorders play an important part in the onset of neurodegenerative disorders, and an enormous amount of research yielded valuable discoveries but has so far not led to the development of effective treatment strategies for Alzheimer’s disease. Corticotropin-releasing factor (CRF) is one of the major hormones and at the same time a neuropeptide acting in stress response. Deregulation of protein levels of CRF is involved in the pathogenesis of Alzheimer’s disease, but little is known about the precise roles of CRF and its binding protein, CRF-BP, in neurodegenerative diseases. In this review, we summarize the key evidence for and against the involvement of stress-associated modulation of the CRF system in the pathogenesis of Alzheimer’s disease and discuss how recent findings could lead to new potential treatment possibilities in Alzheimer’s disease by using CRF-BP as a therapeutic target.

Adenylyl Cyclase Activity in Postmortem Human Brain: Evidence of Altered G Protein Mediation in Alzheimer's Disease

1992 ◽  
Vol 58 (4) ◽  
pp. 1409-1419 ◽  
Author(s):  
Richard F. Cowburn ◽  
Cora O'Neill ◽  
Rivka Ravid ◽  
Irina Alafuzoff ◽  
Bengt Winblad ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Adenylyl Cyclase ◽  
G Protein ◽  
Cyclase Activity ◽  
Adenylyl Cyclase Activity ◽  
Postmortem Human Brain

scholarly journals Integrative glycoproteomics reveals protein N-glycosylation aberrations and glycoproteomic network alterations in Alzheimer’s disease

2020 ◽  
Vol 6 (40) ◽  
pp. eabc5802
Author(s):  
Qi Zhang ◽  
Cheng Ma ◽  
Lih-Shen Chin ◽  
Lian Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Large Scale ◽  
Site Occupancy ◽  
Glycosylation Site ◽  
System Level ◽  
Disease Signatures ◽  
And Control

Protein N-glycosylation plays critical roles in controlling brain function, but little is known about human brain N-glycoproteome and its alterations in Alzheimer’s disease (AD). Here, we report the first, large-scale, site-specific N-glycoproteome profiling study of human AD and control brains using mass spectrometry–based quantitative N-glycoproteomics. The study provided a system-level view of human brain N-glycoproteins and in vivo N-glycosylation sites and identified disease signatures of altered N-glycopeptides, N-glycoproteins, and N-glycosylation site occupancy in AD. Glycoproteomics-driven network analysis showed 13 modules of co-regulated N-glycopeptides/glycoproteins, 6 of which are associated with AD phenotypes. Our analyses revealed multiple dysregulated N-glycosylation–affected processes and pathways in AD brain, including extracellular matrix dysfunction, neuroinflammation, synaptic dysfunction, cell adhesion alteration, lysosomal dysfunction, endocytic trafficking dysregulation, endoplasmic reticulum dysfunction, and cell signaling dysregulation. Our findings highlight the involvement of N-glycosylation aberrations in AD pathogenesis and provide new molecular and system-level insights for understanding and treating AD.

scholarly journals Integrative genomics approach identifies conserved transcriptomic networks in Alzheimer’s disease

2019 ◽  
Author(s):  
Samuel Morabito ◽  
Emily Miyoshi ◽  
Neethu Michael ◽  
Vivek Swarup
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Human Brain ◽  
Association Studies ◽  
Brain Regions ◽  
Genome Wide Association Studies ◽  
Integrative Genomics ◽  
Cell Type ◽  
Postmortem Human Brain ◽  
Cell Transcriptome

AbstractAlzheimer’s disease (AD) is a devastating neurological disorder characterized by changes in cell-type proportions and consequently marked alterations of the transcriptome. Here we use a data-driven systems biology approach across multiple cohorts of human AD, encompassing different brain regions, and integrate with multi-scale datasets comprising of DNA methylation, histone acetylation, transcriptome- and genome-wide association studies as well as quantitative trait loci to define the genetic architecture of AD. We perform co-expression network analysis across more than twelve hundred human brain samples, identifying robust AD-associated dysregulation of the transcriptome, unaltered in normal human aging. We further integrate co-expression modules with single-cell transcriptome generated from 27,321 nuclei from postmortem human brain to identify AD-specific transcriptional changes and assess cell-type proportion changes in the human AD brain. We also show that genetic variants of AD are enriched in a glial AD-associated module and identify key transcription factors regulating co-expressed modules. Additionally, we validate our results in multiple published human AD datasets which are easily accessible using our online resource (https://swaruplab.bio.uci.edu/consensusAD).

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