scholarly journals Investigating Post-translational Modifications in Neuropsychiatric Disease: The Next Frontier in Human Post-mortem Brain Research

2021 ◽  
Vol 14 ◽  
Author(s):  
Melanie J. Grubisha ◽  
Robert A. Sweet ◽  
Matthew L. MacDonald
Keyword(s):  
Gene Expression ◽  
Brain Research ◽  
Research Direction ◽  
Psychiatric Disease ◽  
Post Mortem ◽  
Genetic Studies ◽  
Post Translational Modifications ◽  
Neuropsychiatric Disease ◽  
Post Mortem Brain ◽  
Circuit Function

Gene expression and translation have been extensively studied in human post-mortem brain tissue from subjects with psychiatric disease. Post-translational modifications (PTMs) have received less attention despite their implication by unbiased genetic studies and importance in regulating neuronal and circuit function. Here we review the rationale for studying PTMs in psychiatric disease, recent findings in human post-mortem tissue, the required controls for these types of studies, and highlight the emerging mass spectrometry approaches transforming this research direction.

scholarly journals Single-cell deconvolution of 3,000 post-mortem brain samples for eQTL and GWAS dissection in mental disorders

2021 ◽  
Author(s):  
Yongjin Park ◽  
Liang He ◽  
Jose Davila-Velderrain ◽  
Lei Hou ◽  
Shahin Mohammadi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Genetic Variants ◽  
Cell Types ◽  
Brain Regions ◽  
Post Mortem ◽  
Rna Seq ◽  
Cell Type ◽  
Post Mortem Brain ◽  
Cell Type Specific

AbstractThousands of genetic variants acting in multiple cell types underlie complex disorders, yet most gene expression studies profile only bulk tissues, making it hard to resolve where genetic and non-genetic contributors act. This is particularly important for psychiatric and neurodegenerative disorders that impact multiple brain cell types with highly-distinct gene expression patterns and proportions. To address this challenge, we develop a new framework, SPLITR, that integrates single-nucleus and bulk RNA-seq data, enabling phenotype-aware deconvolution and correcting for systematic discrepancies between bulk and single-cell data. We deconvolved 3,387 post-mortem brain samples across 1,127 individuals and in multiple brain regions. We find that cell proportion varies across brain regions, individuals, disease status, and genotype, including genetic variants in TMEM106B that impact inhibitory neuron fraction and 4,757 cell-type-specific eQTLs. Our results demonstrate the power of jointly analyzing bulk and single-cell RNA-seq to provide insights into cell-type-specific mechanisms for complex brain disorders.

scholarly journals The Neurobiology of Bipolar Disorder: Focus on Signal Transduction Pathways and the Regulation of Gene Expression

2002 ◽  
Vol 47 (2) ◽  
pp. 135-148 ◽  
Author(s):  
Yarema Bezchlibnyk ◽  
L Trevor Young
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Bipolar Disorder ◽  
Protein Kinase ◽  
Regulation Of Gene Expression ◽  
Protein A ◽  
Post Mortem ◽  
Tissue Samples ◽  
Post Mortem Brain ◽  
Transduction Mechanisms

Objective: This article presents an overview of signal transduction path ways and re views the re search under taken to study these systems in clinically relevant samples from patients with bipolar disorder (BD). Method: We re viewed the published findings from studies of post mortem brain tissue and blood samples from patients with BD. Results: Al though the ex act biochemical abnormalities have yet to be identified, the presented findings strongly suggest that BD may be due, at least in part, to abnormalities in signal transduction mechanisms. In particular, altered levels or function, or both, of G-protein a subunits and effector molecules such as protein kinase A (PKA) and protein kinase C (PKC) have consistently been associated with BD both in peripheral cells and in post mortem braintis sue, while more re cent studies implicate disruption in novel second-messenger cascades, such as the ERK/MAPK path way. Conclusions: De spite the difficulties inherent in biochemical studies of clinically relevant tissue samples, numerous investigations have illuminated the signal transduction mechanisms in patients with BD. These studies also suggest that BD may be due to the interaction of many abnormalities. In this con text, novel techniques enabling the study of gene expression promise to assist in untangling these complex interactions, through visualizing the end result of these changes at the level of gene transcription.

scholarly journals Gene expression of tryptophan hydroxylase 2 in post-mortem brain of suicide subjects

2005 ◽  
Vol 9 (01) ◽  
pp. 21 ◽  
Author(s):  
Vincenzo De Luca ◽  
Olga Likhodi ◽  
Hubert H. M. Van Tol ◽  
James L. Kennedy ◽  
Albert H. C. Wong
Keyword(s):  
Gene Expression ◽  
Tryptophan Hydroxylase ◽  
Post Mortem ◽  
Tryptophan Hydroxylase 2 ◽  
Post Mortem Brain

A Review on Important Histone Acetyltransferase (HAT) Enzymes as Targets for Cancer Therapy

2019 ◽  
Vol 15 (2) ◽  
pp. 120-130
Author(s):  
Mohammad Ghanbari ◽  
Reza Safaralizadeh ◽  
Kiyanoush Mohammadi
Keyword(s):  
Gene Expression ◽  
Histone Acetyltransferase ◽  
Critical Role ◽  
Cancer Treatments ◽  
Control Of Gene Expression ◽  
Post Translational Modifications ◽  
Therapeutic Drugs ◽  
The Status ◽  
Acetyl Group ◽  
Increase Gene Expression

At the present time, cancer is one of the most lethal diseases worldwide. There are various factors involved in the development of cancer, including genetic factors, lifestyle, nutrition, and so on. Recent studies have shown that epigenetic factors have a critical role in the initiation and development of tumors. The histone post-translational modifications (PTMs) such as acetylation, methylation, phosphorylation, and other PTMs are important mechanisms that regulate the status of chromatin structure and this regulation leads to the control of gene expression. The histone acetylation is conducted by histone acetyltransferase enzymes (HATs), which are involved in transferring an acetyl group to conserved lysine amino acids of histones and consequently increase gene expression. On the basis of similarity in catalytic domains of HATs, these enzymes are divided into different groups such as families of GNAT, MYST, P300/CBP, SRC/P160, and so on. These enzymes have effective roles in apoptosis, signaling pathways, metastasis, cell cycle, DNA repair and other related mechanisms deregulated in cancer. Abnormal activation of HATs leads to uncontrolled amplification of cells and incidence of malignancy signs. This indicates that HAT might be an important target for effective cancer treatments, and hence there would be a need for further studies and designing of therapeutic drugs on this basis. In this study, we have reviewed the important roles of HATs in different human malignancies.

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