What are mitochondria?
Mitochondria are compartmentalized, dual-membrane organelles that are responsible for most energy production in the cell. Mitochondria contain their own DNA and ribosomes (RNA). Their primary function is to convert energy from glucose into ATP via oxidative phosphorylation. Mitochondria also play an important role in the cellular stress response through processes such as autophagy, apoptosis, and hypoxia. Mitochondrial dysfunction is implicated in many human diseases including cancer, metabolic syndrome & neurodegenerative disorders, ex. Alzheimer’s Disease (AD) (Retrieved from https://www.novusbio.com/research-areas/cellular-markers/mitochondrial-markers.html; https://www.frontiersin.org/articles/10.3389/fnmol.2018.00393/full).
Mitochondria have been increasing recognized as important players in the aging process. Most aging related diseases and particularly neurodegenerative diseases have mitochondrial involvement. Co-activation- brings the neurons to activation and stimulation of mitochondrial production within the cells which helps build more efficient, proactive neuronal networks and plasticity. Mitochondria are the principal synergetic energy generators of cells, and neurons are cells that require a lot of energy. People with depression have fewer mitochondria in their neurons and people with untreated depression have lower levels of protein produced by mitochondria. These help maintain optimal energy production as well as structural integrity and optimal numbers of mitochondria. [Retrieved from https://www.mdpi.com/journal/biology/special_issues/Mitochondria; https://neurosciencenews.com/mitochondira-depression-19710/; https://www.frontiersin.org/articles/10.3389/fnins.2018.00386/full].
A characteristic of diseases such as Alzheimer’s and Parkinson’s—collectively known as neurodegenerative diseases—is the build-up of misfolded proteins. These proteins, such as amyloid and tau in Alzheimer’s disease, form ‘aggregates’ that can cause irreversible damage to nerve cells in the brain. Protein folding is a normal process in the body, and in healthy individuals, cells carry out a form of quality control to ensure that proteins are correctly folded and that misfolded proteins are destroyed. But in neurodegenerative diseases, this system becomes impaired, with potentially devastating consequences. As the global population ages, an increasing number of people are being diagnosed with dementia, making the search for effective drugs ever more urgent. However, progress has been slow, with no medicines yet available that can prevent or remove the build-up of aggregates. [Retrieved from https://neurosciencenews.com/stressed-cells-dementia-protein-folding-20532/].
Where is the vitamin D receptor?
In humans, the vitamin D receptor is encoded by the VDR gene located on chromosome 12q13. 11. Like the iNKT cells, there are also fewer CD8αα/TCRαβ precursors in the thymus of VDR-KO animals. Moreover, to complete development CD8αα/TCRαβ cells must travel from the thymus to the gastrointestinal tract where IL-15 induces proliferation and upregulation of CD8αα. Due to decreased levels of IL-15 receptor expression VDR-KO CD8αα/TCRαβ cells proliferate poorly, resulting in a diminished mature CD8αα/TCRαβ population in the VDR-KO gut (Yu et al., 2008; Bruce and Cantorna, 2011; Ooi et al., 2012). These data illustrate that in contrast to conventional T cells, VDR expression is mandatory for development of both iNKT cells and CD8αα/TCRαβ T cells. VDR is expressed in most tissues of the body, and regulates transcription of about 900 genes involved in intestinal and renal transport of calcium and other minerals. In a study by Patel et al. (1995) plasma toxins from uremic patients was shown to bind to the patient’s VDR, thereby disrupting binding of VDR-RXR to DNA resulting in a diminished VDR response. It so appears that post-translational modifications of VDR adjust VDR activity in both health and disease. [Retrieved from https://www.frontiersin.org/articles/10.3389/fimmu.2013.00148/full].
Note: In humans, the vitamin D receptor is encoded by the VDR gene located on chromosome 12q13. 11. VDR is expressed in most tissues of the body, and regulates transcription of genes involved in intestinal and renal transport of calcium and other minerals (See asc, adhd, epilipsry and schzophrinia & Chromosome 12 above). [Retrieved from https://pubmed.ncbi.nlm.nih.gov/9379138/].
Similarly, early last year, researchers from institutes in Germany and Greece reported a mechanism in the brain’s outer cortical cells that produces a novel ‘graded’ signal all on its own, one that could provide individual neurons with another way to carry out their logical functions. By measuring the electrical activity in sections of tissue removed during surgery on epileptic patients and analyzing their structure using fluorescent microscopy, the neurologists found individual cells in the cortex used not just the usual sodium ions to ‘fire’, but calcium as well. [Retrieved from https://www.sciencealert.com/a-never-before-seen-type-of-signal-has-been-detected-in-the-human-brain?fbclid=IwAR3sZiK3xsrIVnHirG-RjcIKY9NW5czdUk3iPK8dURZnz-qXaKsXJwE6sDs].
The epigenome and transcriptome of VDR-expressing cells is directly affected by vitamin D. Vitamin D target genes encode for proteins with a large variety of physiological functions, ranging from the control of calcium homeostasis, innate and adaptive immunity, to cellular differentiation. This review will discuss VDR’s binding to genomic DNA, as well as its genome-wide locations and interaction with partner proteins, in the context of chromatin. This information will be integrated into a model of vitamin D signaling, explaining the regulation of vitamin D target genes. [Retrieved from https://pubmed.ncbi.nlm.nih.gov/35405966/].
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