My Elbert: NDD’s and Neurotoxicity

Metal-based Toxicity

Environmental degradation is a process through which the natural environment is compromised in some way, reducing biological diversity and the general health of the environment. This process can be entirely natural in origin, or it can be accelerated or caused by human activities. The major causes of the environmental degradation are modern urbanization, industrialization, over-population growth, deforestation etc. Environmental pollution refers to the degradation of quality and quantity of natural resources. [Retrieved from Here…Read more below].

Researchers at Gladstone Institute, have found that calm reduces levels of the protein tau, which is known for its role in Alzheimer’s disease and other neurodegenerative conditions, changes excitatory and inhibitory cells in ways that make it harder for the brain to burst with overexcitation. It also promotes the maintain balance in the brain. Previously they showed in mouse models that reducing tau levels makes the brain more resistant to epilepsy of diverse causes. [Retrieved form https://www.sciencedaily.com/releases/2021/10/211019223309.htm].

” Retrieved from https://www.ncbi.nlm.nih.gov/gene/2904; https://www.medicalnewstoday.com/articles/260649#link; https://ww.eurekalert.org/news-releases/675909#.YTTkWdpAnSc.twitter; https://medcraveonline.com/MOJPB/dna-the-phantom-effect-quantum-hologram-and-the-etheric-body;html?fbclid=IwAR199BUqYjWCvNGq2GCgdzl3d0n_lVzu_6na4KVVcYVuBzk-JeiM-CgRyDQ;

Cell–cell interactions (CCIs) are physical interactions between two or more cells, which can be mediated by proteins, ligands, sugars or other biomolecules. Protein–protein interactions (PPIs) are physical interaction between two proteins, often involved in structural systems, signal transduction or metabolic processes. Differentially Expressed Genes are identified as more highly (or lowly) expressed in one condition versus the other after comparison of their expression values between two conditions. Genes with restricted, constitutive or unusual pattern of expression are quantified accordingly to their characteristics to avoid miscalculation or underestimation of signals. Operational taxonomic unita definition used to classify groups of closely related organisms. DNA sequences can be clustered according to their similarity to one another, and operational taxonomic units are defined based on the similarity threshold (usually 97% similarity) set by the researcher. Biomolecules or biological molecule, any of numerous substances that are produced by cells and living organisms. (Retrieved from https://www.hindawi.com/journals/ijg/2003/393029/; https://www.nature.com/articles/s41576-020-00292-x#Sec22)

Note: Iron molecules are found in a variety of different chemical environments in biology. In addition, iron biomolecules can be divided into those which utilise iron to effect a biological function (02 transport, electron shuttling, etc.) and those which transport and store iron. With regards to Parkinson’s Disease, one of the targets that LRRK2 regulates is called Rab8a, a protein which, along with many others of the Rab family, helps control the movement or “trafficking” of a wide variety of cellular vesicles (vesicle is a structure within or outside a cell, membrane-bound subcellular compartments). [Retrieved from https://neurosciencenews.com/parkinsons-diseaseiron-19808/].

Nerve cells in the human brain talk to one another at sites called synapses, where molecules are released to signal to the next cell. When people learn or remember things, this signalling is strengthened. When communication between synapses goes wrong, circuits become broken. The function of nerve cells and synapses depends on proteins that are made using information encoded in genetic material called RNA. It is thought that RNAs are located exactly where and when they are needed for synaptic signalling because some kind of synaptic ‘tag’ labels the correct active synapse. Scientists have recently learned that RNA can have a methyl group/molecule added to one of the RNA bases, which ‘marks’ the RNA message. Such adding of methyl groups can influence proteins binding to DNA or RNA and consequently stop proteins being produced.[Retrieved from https://kids.frontiersin.org/articles/10.3389/frym.2017.00039].

A new study shows that RNA marking can be reversed at synapses and hence may act as a ‘synaptic tag’. Synaptic tagging allows the synapse, rather than the nucleus, to be the unit of long-lasting neuronal plasticity. The findings suggest, that if disrupted, this could cause synapses and nerve cells to malfunction by influencing the formation of toxic protein clumps [causing brain injury (deficits) such in the case of Long-Term Potentiation (LTP) and long-term memory (LTM) encoding needed for learning.

The genomic mechanisms involve methyl groups being put on RNA messages and importantly taken off when a synapse is active. The implications are very important for normal brain function, but also for reversible psychiatric mental conditions such as anxiety and addiction disorders and early-stage neurodegenerative diseases such as dementias.” [Retrieved from https://neurosciencenews.com/synapse-neurotransmission-19501/; https://www.frontiersin.org/articles/10.3389/fnhum.2013.00589/full?utm_source=newsletter&utm_medium=email&utm_campaign=Neuroscience-w41-2013].

Note: Iron is part of the Heme group which plays multiple roles in cellular processes. The strong affinity of heme toward oxygen makes it possible for hemoglobin and myoglobin, two heme-containing proteins, to function as major oxygen transporters. Heme also participates in respiration, sensing of diatomic gases, drug detoxification, signal transduction and regulation of transcription, translation, microRNA processing, mitochondrial protein import, protein stability, and differentiation. While most cells synthesize heme, differentiating erythrocytes represent the major site of heme production in humans due to the synthesis of hemoglobin, which accounts for 85% of the total heme. Malfunction of heme synthesis can lead to disorders such as anemia and porphyrias. [Retrieved from https://www.sciencedirect.com/topics/chemistry/heme].

Also, Note: Studies have demonstrated that iron can regulate tau.This study examines the levels of total tau, hyperphosphorylation of tau, and SDS- and β-mercaptoethanol-resistant high molecular weight tau (HMW-tau) in crude extracts from gray and white matters of AD frontal lobes were analyzed by immuno-blots. They found the seeding potency is markedly higher in gray matter than in white matter such disease that includes Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), and other disease pathologies ..[Retrieved from https://pubmed.ncbi.nlm.nih.gov/33459649/; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108061/].

Iron chelation therapy, either subcutaneous or orally administered, has been used successfully in various clinical conditions. The removal of excess iron from various tissues, e.g., the liver spleen, heart, and the pituitary, in beta thalassemia patients, has become an essential therapy to prolong life. More recently, the use of deferiprone to chelate iron from various brain regions in Parkinson’s Disease and Friederich’s Ataxia has yielded encouraging results, although the side effects, in <2% of Parkinson’s Disease(PD) patients, have limited its long-term use. A new class of hydroxpyridinones has recently been synthesised, which showed no adverse effects in preliminary trials. A vital question remaining is whether inflammation may influence chelation efficacy, with a recent study suggesting that high levels of inflammation may diminish the ability of the chelator to bind the excess iron. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789569/; https://pubmed.ncbi.nlm.nih.gov/33805195/; https://pubmed.ncbi.nlm.nih.gov/12127956/; https://www.verywellhealth.com/what-is-iron-chelation-4103177:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4486448/;https://ashpublications.org/blood/article/116/21/2064/111868/Combination-of-Two-Orally-Active-Iron-Chelating].

Synergism

Synergism represents an efficient means of increasing the amplitude of cellular responses induced by low levels of stimulation. Recently, several kinetic and physicochemical models have been developed to describe and predict synergistic responses. Synergy mainly results from mutations in functionally related genes. In one study, on the etiology of the prevalent defects found with Antiphospholipid Syndrome (APS), a systemic autoimmune disease which has cognitive effects, the synergism between aPL and anti-NMDA antibodies were explored and found a direct effect of anti-PL on neuronal cells. [Retrieved from https://pubmed.ncbi.nlm.nih.gov/19665253/; https://www.frontiersin.org/articles/10.3389/fimmu.2016.00005/full]. Note: physicochemical models include physicochemical stress(es) comprises environmental factors in the form of food/nutrition, noise, pollution, metabolic disorder, infection, and inflammation. [Retrieved from https://www.frontiersin.org/research-topics/5755/stress-and-immunity].

In recent years, large genome-wide association studies have been extremely helpful to identify new genetic risks of psychiatric diseases (e.g. PTSD, SCZ, BP, MDD), and genetic overlapping risks among these disorders and other medical diseases, and traits. A more comprehensive understanding of the genetic overlapping among these disorders is needed to clarify common pathways among diseases, or specific genes (see The Thymus below) uniquely implicated in each disorder. [Retrieved from https://www.frontiersin.org/research-topics/15833/shared-genetic-risk-factors-among-psychiatric-diseases-and-other-medical-diseases-and-traits]

Biological scientists often want to determine whether two agents or events, for example, extracellular stimuli and/or intracellular signaling pathways, act synergistically when eliciting a biological response. Similarly, the nervous system is highly vulnerable to various internal and external factors which could lead to acute or chronic neurodegeneration. The morphological basis of dysfunction after injury involves loss of integrity of the extracellular matrix, neuronal circuitry, and synaptic activity and plasticity (see Thymus below).

“Light Of The Soul”

Yes, I do believe the disconnect for families and schools. It’s in the Spiritual Development. The disconnect happens in these domains such as: (intellectual) what is right, (moral) what is good, and (imaginative) what is His Divine Will for us by in and upon design, plan, and purpose!!! The primary injury enables a huge variety of developmentally-related biomolecules (carbohydrates, lipids, nucleic acids, and proteins) to stimulate the process of regeneration. Extracellular proteins, cell adhesion molecules, neurotrophic factors as well as different organic and inorganic compounds of the nervous tissue are necessary for recovery after injury. However, the secondary injury as well as further degeneration of the surrounding tissue, could be prevented by reactivation and recruitment of a plethora of cell signals, such as growth factors, neurotransmitters, extracellular matrix (see thymus below) proteases, cell adhesion and recognition molecules (search Agents for Metal-Based Drugs and Chelating metal-based therapies for tauopathies for Neurodegenerative Diseases; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821171/). [Retrieved from https://www.frontiersin.org/research-topics/12990/morphogenic-cascades-underlying-regeneration-and-plasticity-after-nervous-system-injury; https://www.sciencedirect.com/science/article/abs/pii/S0022282898906551; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6514778/].

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Published by Tricia Cook, MEd., Online Dyslexia and Behavioral Interventionist, RSP, AA O-G Tutor & Montessorian

My interest is in helping parents and teachers to understand learning and behavioral challenges and to love learning again. I graduated from Auburn in ECE in 1998. I have been a Montessori teacher here in Birmingham for almost 12 years and have lived in Birmingham for the past 19 years. As an early childhood teacher, I want continue to grow and develop as a constant learner. In 2012, I graduated from Secondary Education with a P-12 Reading Specialist certification the University of Alabama. As a Reading Specialist, I train on diversity and literacy development; I have a specialized knowledge of assessment and diagnosis that is vital for developing, implementing, and evaluating your literacy and neurodiversity behavioral, character development programing. Also, I have varying experiences designing instruction and environments for Montessori and Non-Montessori (OSR-Pre-K) environments. Therefore, I can consult for any environment or setting! In 2013, I attained my highly qualified status in ECE and Reading. In 2013, I also got my Orton-Gillingham AA tutor certification. I currently tutor full-time along with consulting. I have actually been tutoring since 2003. Along with other independent tutoring/interventionist experiences, I have brought dozens of students from an emergent to an advanced reading level! In addition to tutoring, I have provided the reading strengths and needs of my students and share that information to classroom teachers, parents, specialized teachers, and other stakeholders.  Lastly, I have also been a trainer/presenter, since 2008 and really enjoy this aspect of my career. As an experienced trainer, I have trained on many topics including: literacy (the five components), classroom management, positive discipline, diversity character development, Montessori Philosophy, policies and procedures, child development, and Alabama's Pre-k. Take note: Schools and families are desperately looking for an alternative type of affordable multi-sensory, hands-on, and interesting instruction. Currently, I am training and interested in writing on the following topics: A Comparison of Pre-K to Kindergarten; Adolescent Literacy (7th+); Assessment; Developing Readers; Children’s Literature; Classroom Management Techniques; Comprehension; Montessori Philosophy; Environmental Print & Early Writing; Family Attachment; Language and Literacy; Outdoor Classroom; Poetry Writing (7th+); Positive Guidance; Fine-motor Development; Cursive Writing; Creative Writing; Comprehension: Study Skills/Test Taking Strategies; Morphology; Phonics Instruction; Diversity Education; Neurodiversity Education; HandWriting; Reading Strategies; Best Practices P-12. Thank you, Tricia Cook, MEd., RSP, AOG; https://linktr.ee/tcooktutor

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