What does it take to cure the brain? Studies Toward Genes, Proteins, Processes, and Rehabilitation

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Background

Curation of the brain is a complex matter. For starters, all types of brain cells are involved : neurons, astroglia, and microglia, oligodendrocytes , and endothelial cells. This curation requires counteracting infections, oxidative stress, inflammatory responses, cell degeneration, and cell death, while promoting cell regeneration and tissue regeneration. And in the end to reestablish function. This implies that myriads of molecular biological intracellular processes are involved. Even conditions extending beyond the central nervous system are more than just relevant, in the cardiovascular system, the immune system, the endocrine system and, most surprisingly maybe, the essential participation of the microbiota in the intestinal system. Intuitively, one would expect that restoration of tissue and function is relatively more effective at young ages, compared to more advanced ages.

Genomics, Proteinomics, and Pathway Analysis let us see how the myriads of processes at various levels, from molecular biological to tissues and organs, are involved in brain injury and healing. Artificial Intelligence can tell us how the complexity of data is organized. In this way also the phenomenon of "one treatment – multitarget effects" can be better appreciated. As examples for these multitarget effects, efficacious curative TSPO ligands modulate mitochondrial functions, and via the mitochondria - cell nucleus signaling pathway they can also modulate expression of cell nuclear genes and thereby regulate the various pathways for efficacious brain curation. Specific estrogen receptor modulators (SERMs) do the same via actions on alpha and beta estrogen receptors located in the cell nucleus as well as in the mitochondria. Fucoidans appear to be able to accomplish this via modulation of Sirtuins that in turn act on mitochondria as well as the cell nucleus. Other efficacious curative agents, such as stem cell and secretome applications, gene therapy, even behavioral therapies, also appear to affect multiple targets in the cell. This kind of knowledge enables the neuroscience community to continually improve and discover novel treatments that may give us a grip on the multifaceted processes underlying curation of brain damage.

One could ask the question whether a healing process is a self-organizing process, or whether it is a preprogrammed system. To touch on this shortly, in fish, for example zebrafish, excised brain regions and their architecture can be regenerated completely, and also in birds brain areas can be seasonally lost and rebuilt. Questions that can be asked at this stage :
1) One can wonder whether in mammals and thus humans, similar processes can be activated.
2) The central question of course is whether such processes can restore brain damage and brain functions after brain damage caused by disease, injury, and aging.
3) Are cellular and histological brain recovery and cognitive and behavioral restoration closely linked?
4) Furthermore, as continuing data accumulation is incessant, pattern recognition ( integration of the accumulated data ) has to be improved. This, for example, can be done with the aid of Artificial Intelligence.
5) Also of most practical importance is the discovery of adequate vehicles to dissolve efficacious drugs. In particular, such vehicles should allow drugs to be transported via the hydrophilic bloodstream and to cross the lipophilic blood-brain barrier.
6) Does one size fit all ? Are different types of treatment required for each brain disease and injury ? Will treatments be similarly effective in the young and the old ?

Thus, in summary, any agent for treatment to cure brain problems needs a combination of being hydrophilic, lipophilic, and multitarget to reach and enter the brain and to modulate the numerous molecular biological mechanisms and substrates that underlie the injurious as well as the curative processes in the brain.

Keywords: brain damage, treatmen, brain injury, aging, artificial intelligence, drugs

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