Brain local and regional neuroglial alterations in Alzheimers Disease: cell types, responses and implications.

Epithelial cells exfoliated in human urine can include cells anywhere from the urinary tract and kidneys; however, podocytes and proximal tubular epithelial cells (PTECs) are by far the most relevant cell types for the study of genetic kidney diseases. When maintained in vitro, they have been proven extremely valuable for discovering disease mechanisms and for the development of new therapies. Furthermore, cultured patient cells can individually represent their human sources and their specific variants for personalized medicine studies, which are recently gaining much interest. In this review, we summarize the methodology for establishing human podocyte and PTEC cell lines from urine and highlight their importance as kidney disease cell models. We explore the well-established and recent techniques of cell isolation, quantification, immortalization and characterization, and we describe their current and future applications.

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Sortilin expression and uptake of α-galactosidase A: A general mechanism of endocytosis in Fabry disease cell types

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2015.12.439 ◽

2016 ◽

Vol 117 (2) ◽

pp. S106

Author(s):

Jin-Song Shen ◽

Taniqua S. Day ◽

Xing-Li Meng ◽

Zhi-Ping Liu ◽

Raphael Schiffmann

Keyword(s):

Fabry Disease ◽

Cell Types ◽

General Mechanism ◽

Disease Cell

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High extracellular lactate increases reductive carboxylation in breast tissue cell lines grown under normoxic conditions

10.1101/558296 ◽

2019 ◽

Author(s):

Arthur Nathan Brodsky ◽

Daniel C. Odenwelder ◽

Sarah W. Harcum

Keyword(s):

Breast Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cell Types ◽

Metabolic Reaction ◽

Lactate Accumulation ◽

Extracellular Lactate ◽

Disease Cell ◽

Reductive Carboxylation ◽

High Lactate

AbstractIn cancer tumors, lactate accumulation was initially attributed to high glucose consumption associated with the Warburg Effect. Now it is evident that lactate can also serve as an energy source in cancer cell metabolism. Additionally, lactate has been shown to promote metastasis, generate gene expression patterns in cancer cells consistent with “cancer stem cell” phenotypes, and result in treatment resistant tumors. Therefore, the goal of this work was to quantify the impact of lactate on metabolism in three breast cell lines (one normal and two breast cancer cell lines – MCF 10A, MCF7, and MDA-MB-231), in order to better understand the role lactate may have in different disease cell types. Parallel labeling metabolic flux analysis (13C-MFA) was used to quantify the intracellular fluxes under normal and high extracellular lactate culture conditions. Additionally, high extracellular lactate cultures were labelled in parallel with [U-13C] lactate, which provided qualitative information regarding the lactate uptake and metabolism. The 13C-MFA model, which incorporated the measured extracellular fluxes and the parallel labeling mass isotopomer distributions (MIDs) for five glycolysis, four tricarboxylic acid cycle (TCA), and three intracellular amino acid metabolites, predicted lower glycolysis fluxes in the high lactate cultures. All three cell lines experienced increased reductive carboxylation of glutamine to citrate in the TCA cycle as a result of high extracellular lactate. Increased reductive carboxylation previously has been observed under hypoxia and other mitochondrial stresses, whereas these cultures were grown aerobically. In addition, this is the first study to investigate the intracellular metabolic responses of different stages of breast cancer progression to high lactate exposure. These results provide insight into the role lactate accumulation has on metabolic reaction distributions in the different disease cell types while the cells are still proliferating in lactate concentrations that do not significantly decrease exponential growth rates.

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Staging of α-synuclein in the olfactory bulb in a model of Parkinson's disease: Cell types involved

Movement Disorders ◽

10.1002/mds.23197 ◽

2010 ◽

Vol 25 (11) ◽

pp. 1701-1707 ◽

Cited By ~ 19

Author(s):

Isabel Ubeda-Bañon ◽

Daniel Saiz-Sanchez ◽

Carlos de la Rosa-Prieto ◽

Alicia Mohedano-Moriano ◽

Noelia Fradejas ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Olfactory Bulb ◽

Cell Types ◽

Disease Cell

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Neurons burdened by DNA double strand breaks incite microglia activation through antiviral-like signaling in neurodegeneration.

10.1101/2021.12.23.474002 ◽

2021 ◽

Author(s):

Gwyneth M Welch ◽

Carles Adsera Boix ◽

Eloi Schmauch ◽

Jose Davila-Velderrain ◽

Matheus B. Victor ◽

...

Keyword(s):

Brain Tissue ◽

Cell Types ◽

Double Strand Breaks ◽

Microglia Activation ◽

Slice Culture ◽

Immune Gene ◽

Dna Double Strand Breaks ◽

Alzheimers Disease ◽

Strand Breaks ◽

Immune Pathways

DNA double strand breaks (DSBs) are linked to aging, neurodegeneration, and senescence. However, the role played by neurons burdened with DSBs in disease-associated neuroinflammation is not well understood. Here, we isolate neurons harboring DSBs from the CK-p25 mouse model of neurodegeneration through fluorescence-activated nuclei sorting (FANS), and characterize their transcriptomes using single-nucleus, bulk, and spatial sequencing techniques. We find that neurons harboring DSBs enter a late-stage DNA damage response marked by the activation of senescent and antiviral-like immune pathways. We identify the NFkB transcription factor as a master regulator of immune gene expression in DSB-bearing neurons, and find that the expression of cytokines like Cxcl10 and Ccl2 develop in DSB-bearing neurons before glial cell types. Alzheimers Disease pathology is significantly associated with immune activation in excitatory neurons, and direct purification of DSB-bearing neurons from Alzheimers Disease brain tissue further validates immune gene upregulation. Spatial transcriptomics reveal that regions of brain tissue dense with DSB-bearing neurons also harbor signatures of inflammatory microglia, which is ameliorated by NFkB knock down in neurons. Inhibition of NFkB or depletion of Ccl2 and Cxcl10 in DSB-bearing neurons also reduces microglial activation in organotypic brain slice culture. In conclusion, we find that in the context of age-associated neurodegenerative disease, DSBs activate immune pathways in neurons, which in turn adopt a senescence associated secretory phenotype to elicit microglia activation. These findings highlight a novel role for neurons in the mechanism of age-associated neuroinflammation.

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Does Green Tea Induce Hormesis?

Dose-Response ◽

10.1177/1559325820936170 ◽

2020 ◽

Vol 18 (3) ◽

pp. 155932582093617 ◽

Cited By ~ 2

Author(s):

Edward J. Calabrese ◽

Aristidis Tsatsakis ◽

Evgenios Agathokleous ◽

James Giordano ◽

Vittorio Calabrese

Keyword(s):

Green Tea ◽

Dose Response ◽

Low Dose ◽

Optimal Dose ◽

Cell Types ◽

Human Populations ◽

Neural Cells ◽

Experimental Protocols ◽

Dose Responses ◽

Disease Cell

Green tea, and its principal constituent (–)-epigallocatechin-3-gallate (EGCG), are commonly shown to induce biphasic concentration/dose responses in a broad range of cell types, including non-tumor cells, and tumor cell lines. The most active area of research dealt with an assessment of neural cells with application to neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease cell models, often using preconditioning experimental protocols. The general findings demonstrate EGCG-induced hormetic effects resulting in an enhanced acquired resilience within an adaptive and temporally dependent homeodynamic framework. The biphasic dose responses displayed the typical quantitative features of the hormetic dose response with respect to the amplitude and width of the stimulatory response. These findings provide further evidence for the general occurrence of hormetic dose responses with such responses being independent of the biological model, end point, inducing agent, and mechanism. The biphasic nature of these responses has important implications since it suggests optimal dose ranges for end points of public health and therapeutic applications. These findings indicate the need to assess the entire dose-response continuum in order to better define the nature of the dose response, especially in the low-dose zone where such exposures are common in human populations.

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