DPP4 Valorphin Activate NR4As Pathway and OPA1 That Protect from CoQ10 Deficiency, OPA1 Dysfunctions and WMH
Authors:   Biomedical Molecular Studies, Toronto Canada and Cairo Egypt, El Tantawi Ashraf Marzouk 
Published: November 2023

Deficiencies in Threonine (Thr), Tryptophan hydroxylase (Tph), Glutamate (Glu), Glutamine (Gln), and Leucine can result from increased polarizability in mTORC1 and its subunits. These deficiencies may lead to disorders in OPA1 repair, which can be a primary cause of Coenzyme Q10 (CoQ10) deficiency disease. CoQ10 is crucial for maintaining the inner mitochondrial membrane and is necessary for the synthesis of the glucocorticoid receptor (GCR). Mitochondrial damage or dysfunction can lead to the accumulation of pro-inflammatory molecules, which may cause mutations in subunits and proteins. Reduced levels of Tryptophan, Glycine (Gly), and Arginine (Arg) can result in decreased Proline synthesis, subsequently reducing tRNA levels. This, in turn, can impair mitochondrial OPA1 repair and function due to decreased GTPase activity. The reduced function of GTPase can lead to decreased IL-17 synthesis and the accumulation of pro-inflammatory molecules, resulting in a reduction in serotonin production, as well as decreased production of GCbeta, oxytocin, and Nrf2. These changes can lead to a decrease in the proliferation of megakaryocytes and, consequently, reduced hematopoiesis, which is associated with white matter hyperintensity. Opioid receptors play a role in producing powerful analgesia, contributing to the function of immune cells, and modulating acquired immune responses, including the function of lymphocytes. Tryptophan, Leucine, and Tyrosine kinases are crucial for activating mitochondrial OPA1 repairs, which are essential for CoQ10 synthesis. Tryptophan (TGG) is necessary for activating Proline, which is essential for both OPA1 function and tRNA production. Additionally, it plays a role in IL17 synthesis and the activation of the NR4As pathway, which includes the activation of GCs-beta, oxytocin, and Nrf2 production, respectively. Cytotoxic edema can result from uncontrolled or uncompensated cation influx, primarily sodium (Na+). This edema occurs due to high levels of potassium (K) and sodium (Na) binding toxicity, leading to coagulation and reduced ATPase and GTPase activity. It starts with a decrease in CoQ10 synthesis and an increase in Plasma Glial Fibrillary Acidic Protein (GFAP), resulting in decreased mineralocorticoid. Increased sodium and potassium binding, associated with decreased anions binding in biological molecules, can be due to reduced GTPase and OPA1 function. This reduction in anions function is the result of a primary Coenzyme Q10 (CoQ10) deficiency, leading to elevated GFAP levels in cognitively normal older adults at risk of Alzheimer's disease. Primary Coenzyme Q10 (CoQ10) deficiency is typically associated with multisystem involvement, including neurologic manifestations such as fatal neonatal encephalopathy with hypoxia, late-onset multiple-system atrophy-like symptoms, dystonia, spasticity, seizures, and intellectual disability. Autoimmune diseases and skin inflammatory disorders can start due to increased cation binding toxicity, which reduces ATPase and GTPase function, characterized by a deficiency in proper GTPase production, leading to a reduction in mitochondrial OPA1 function and a deficiency in GCs-beta synthesis via the NR4As pathway. GFAP is an important neuroinflammation biomarker, and an increase in its levels may indicate OPA1 dysfunction, a decrease in CoQ10, neuroinflammation, and a reduction in the NR4As pathway. The increase in GFAP during acute ischemic stroke can be initiated by increased cation binding to anions, leading to enhanced energy stability and decreased tRNA production, which is proline-dependent. This decrease in tRNAs and GTPase activity can result in a decrease in IL17 production, increased inflammation, decreased blood flow to the brain, and reduced oxygen supply to the brain, ultimately contributing to neuronal damage. A decrease in hemorphin (valorphin) reflects reduced lymphocyte function and a loss of cholinecontaining phospholipids (CCPLs). Valorphin contains Tyrosine, which is essential for kinases production, required for choline kinases synthesis, and crucial for activating tRNAs, serotonin, oxytocin, and Nrf2 via the NR4As pathway, all of which are essential for lymphocyte function and antiinflammatory growth. Nrf2 dysfunction, connected to NR4As and oxytocin dysfunction, plays a significant role in the pathogenesis of vascular cognitive impairment and dementia (VCID).