The IPAK Model of ASD Causality (aka "The IPAK Model")
After reviewing thousands of studies over two years, a more complete picture of the causality of ASD has now emerged.
We are working on an interactive web resource to allow the public and researchers to access the scientific literature in support of each component of this ASD causality model.
Note that this model includes an important component of genetic susceptibility, never addressed in whole-population ecological correlational association studies.
Again, the hypothesis of genetic susceptibility has not been addressed.
USAGE: Please use with citation and reference "Personal Communication, Dr. J. Lyons-Weiler, The Institute for Pure and Applied Knowledge" with a link to this webpage.
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Vaccine Metals and ER Stress
Lemire et al., 2009. Aluminum-induced defective mitochondrial metabolism perturbs cytoskeletal dynamics in human astrocytoma cells. J. Neurosci Res 87:1474-83
Vaccine ER Stress + Unfolded Protein ER Stress = ER Hyperstress
Lyons-Weiler, J. 2018. Autism is an Acquired Cellular Detoxification Deficiency Syndrome with Hetergeneous Genetic Predisposition. Autism Open Access, (Publisher's "editing version" online: https://www.omicsonline.org/open-access/autism-is-an-acquired-cellular-detoxification-deficiency-syndrome-with-heterogeneous-genetic-predisposition-2165-7890-1000224.pdf
ER Hyperstress -> Impaired Cellular Detoxification
ER/Mito/Golgi Citations in: Lyons-Weiler, J. 2018. Autism is an Acquired Cellular Detoxification Deficiency Syndrome with Hetergeneous Genetic Predisposition. Autism Open Access, (Publisher's "editing version" online: https://www.omicsonline.org/open-access/autism-is-an-acquired-cellular-detoxification-deficiency-syndrome-with-heterogeneous-genetic-predisposition-2165-7890-1000224.pdf
Leaky Gut -> Absorption of Toxins
De Chambrun G.P., Body-Malapel M., Frey-Wagner I., Djouina M., Deknuydt F., Atrott K., Vignal C. Aluminum enhances inflammation and decreases mucosal healing in experimental colitis in mice. Mucosal Immunol. 2014;7:589–601.
Kirschbaum, BB and C Schoolwerth. 1989. Acute Aluminum Toxicity Associated with Oral Citrate and Aluminum-Containing Antacids. The American Journal of the Medical Science 297:9-11.
Tian F. 2017. The therapeutic protection of a living and dead Lactobacillus strain against aluminum-induced brain and liver injuries in C57BL/6 mice. PLoS One. 12:e0175398. doi: 10.1371/journal.pone.0175398
Yu, L 2017. Lactobacillus plantarum CCFM639 can prevent aluminium-induced neural injuries and abnormal behaviour in mice. Journal of Functional Foods 30:142-150.
Chronic Microglial Activation -> Leaky Gut
Grubišić V and Parpura V. 2015. The second brain in autism spectrum disorder: could connexin 43 expressed in enteric glial cells play a role? Front Cell Neurosci. 9:242. doi: 10.3389/fncel.2015.00242.
Kirchgessner AL et al., 1997. Excitotoxicity in the enteric nervous system. J Neurosci. 17(22):8804-16.
Unfolded Proteins -> Autoimmunity
Immunoneuroexcitotoxicity -> Aberrant Pruning
Cunningham CL et al., 2013. Microglia regulate the number of neural precursor cells in the developing cerebral cortex. J Neurosci. 33(10):4216-33. doi: 10.1523/JNEUROSCI.3441-12.2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3711552/
Fiorentino et al., 2016. Blood–brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Molecular Autism 4:49
Strunecka A., et al. 2018. Immunoexcitotoxicity as the central mechanism of etiopathology and treatment of autism spectrum disorders: A possible role of fluoride and aluminum. Surg Neurol Int. 2018; 9:74.
Aberrant Pruning -> Altered Development
Thomas MS. The over-pruning hypothesis of autism. Dev Sci. 2016 19(2):284-305.
Kim HJ et al. Deficient autophagy in microglia impairs synaptic pruning and causes social behavioral defects. Mol Psychiatry. 2017 22(11):1576-1584.
Vaccine Metals Release -> Autoimmunity
Tomljenovic L, Shaw CA Mechanisms of aluminum adjuvant toxicity and autoimmunity in pediatric populations. Lupus. 2012 21(2):223-30.
Autoimmunity -> Altered Development
Braunschweig D et al., 2008. Autism: maternally derived antibodies specific for fetal brain proteins. Neurotoxicology. 29(2):226-31.
Cabanlit M et al., 2007. Brain-specific autoantibodies in the plasma of subjects with autistic spectrum disorder. Ann N Y Acad Sci. 1107:92-103.
Malkki H. Neurodevelopmental disorders: Maternal antibodies induce autism-like phenotype in mice. Nat Rev Neurol. 2016 12:678-679. doi: 10.1038/nrneurol.2016.165.
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