With the growing epidemic of autism spectrum disorder in children, countless researchers are searching for the genes and pathways which lead to what we call autism. This paper describes how two proteins, Cullin 3 and Plastin 3 contribute to the failure of certain brain cells to find their destination in brain development. In the mouse model, the resulting mislocated brain cells resulted in mice with autistic type behaviors.
As scientists have studied autism, they have realized that the path to autism varies between different individuals. In their work, they have found numerous genes that seem to contribute to autism risk. They have also found various environmental risk factors which also play a role in the epidemic. What they have not found is a pharmaceutical therapy nor a sure-fire preventive therapy. In functional medicine, we have taken their findings and applied them to many children, seeing significant results for such children with autism.
Still, whether in functional or conventional pediatrics, we all eagerly await further and deeper understanding of this disease process as the effects on children’s lives are profound. This study intrigues everyone as we may be drawing a little closer to a root process which can be modulated for prevention and/or therapy.
Researchers linked a protein called Cullin 3 with another protein called Plastin 3. The Cullin 3 operates to mark other proteins in cells for degradation. Without a clean up process, some proteins may accumulate and ultimately cause damage leading to disease; we see this in other neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease.
In a mouse model, dysfunction of the Cullin 3 gene lead to mice with autistic behaviors. With further study, a particular protein called Plastin 3 was found to be elevated in nerve cells of the mice brains. If the accumulation of Plastin 3 was prevented, then nerve ends moved to a different location in the brains and the autistic behaviors did not occur. With a variety of changing variables, the researchers feel confident that this interplay of Cullin 3 and Plastin 3 contribute to whether or not the brain cells move to the correct location near the brain surface rather than remaining deeper in the brain tissue layers. For children with autism, problems with this type of brain cell movement seems connected with the disease.
As we all work towards helping children with autism overcome this disabling condition, understanding these pathways offers hope of a brighter future. Meanwhile, we will continue to optimize our patient’s brain health, lowering inflammation, removing toxins, and increasing important chemicals like brain derived neurotrophic factors. If we can one day also modulate this Cullin 3 – Plastin 3 pathway, we will likely be another step closer to healthier more abundant lives for these children and the adults that they grow into.
Jasmin Morandell, Lena A. Schwarz, Bernadette Basilico, Saren Tasciyan, Georgi Dimchev, Armel Nicolas, Christoph Sommer, Caroline Kreuzinger, Christoph P. Dotter, Lisa S. Knaus, Zoe Dobler, Emanuele Cacci, Florian K. M. Schur, Johann G. Danzl, Gaia Novarino. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-23123-x
Thanks to Science Daily:
Institute of Science and Technology Austria. “Defective gene slows down brain cells.” ScienceDaily. ScienceDaily, 24 May 2021. <www.sciencedaily.com/releases/2021/05/210524091945.htm>.
Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond. We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more... offering the hope of healthier more abundant lives to those with chronic illness.