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The pathogenesis of cerebral palsy

Dr. Nikonov
Dr. Nikonov

The pathogenesis of cerebral palsy from my point of view, confirmed by the discoveries of the Nobel laureates.

 

In 2004, Aaron Ciechanover, Avram Hershko, and Irwin Rose were honored with the highest award, the Nobel Prize in Chemistry "for the discovery of ubiquitin-mediated protein degradation”.

Irwin Rose

Irwin Rose

Avram Hershko

Avram Hershko

Аaron Ciechanover

Аaron Ciechanover

Aaron Ciechanover, Avram Hershko, and Irwin Rose discovered the degradation, that is, splitting of proteins. This process occurs as follows: a protein to be destroyed receives, at some point, a molecular mark, a kind of "kiss of death”. The mark consists of a protein called ubiquitin.

Ubiquitin, in turn, is a polypeptide consisting of 76 amino acids. Its name comes from the Latin word ubique - "everywhere" and means "omnipresent”.

Ubiquitin

It attaches to the protein to be destroyed and accompanies it to the proteasome (the organelle responsible for the destruction of proteins). Ubiquitin is a signal that this protein must be destroyed. Shortly before the protein enters the proteasome, the ubiquitin mark detaches and leaves it for further reuse.

The Nobel Prize winner Yosinori Osumi in 2016 received the Nobel Prize in Medicine and Physiology "for discovering the mechanisms of autophagy”.

Yosinori Osumi

Autophagy suggests absorption of damaged proteins by vesicles (cellular vesicles), called autophagosomes.

Dr. Hugo Bellen

Dr. Hugo Bellen proved that after the vesicles have absorbed excess protein for the muscle cells, they fuse with lysosomes, which acidic medium activates waste-decomposing enzymes. However, the presence of mutant ubiquilin makes the medium in the lysosomes insufficiently acidic to dissolve all the undesired protein found in the vesicle.

Dr. Nikonov
Dr. Nikonov

The muscle cell starts developing protein swelling (this is how I, Nikolai Borisovich Nikonov, call it). Protein swelling changes the structure of the cytoplasm to a denser, which leads to paralysis (tetraparesis, diplegia, paraparesis, hemiplegia).

 

Doctor Nikonov

Dr. Nikonov’s method of working on the muscle cells enhances their chemical processes.

The results are as follows:

  1. The structure of the cytoplasm becomes more liquid.
  2. The number of energy-supplying mitochondria increases.
  3. The amount of acidic enzymes increases in lysosomes, which dissolve the unwanted protein (protein swelling disappears).
  4. The muscle cell begins to move properly (completely stretching and contracting).

De Duv

Lysosomes are the smallest cytoplasmic organelles (0.2–0.4 µm), discovered by De Duve (1949). Lysosomes are corpuscles bounded by a lipid membrane and containing an electron-dense matrix consisting of a set of hydrolytic enzyme proteins (50 hydrolases) able to cleave any polymeric compounds (proteins, lipids, carbohydrates, and their complexes) into monomeric fragments.

Inside the lysosome, there is an enzyme called “acid phosphatase”, which cleaves proteins, nucleic acids, polysaccharides, and lipids.

Lysosomes are surrounded by a lipoprotein membrane, which prevents access of outside substrates to enzymes inside lysosomes.

Acid phosphatase dissolves protein at pH 5.

The acidic medium in lysosomes is provided due to the presence of ATP-dependent H+ pump in their membranes.

The lysosome membrane has the integrated protein carriers used for transporting hydrolysis products from lysosomes into the cytoplasm: monomers of cleaved molecules - amino acids, sugars, nucleotides, and lipids.

Dr. Nikonov
Dr. Nikonov

Why don't these membrane formations digest themselves?

 

Lysosome membrane elements are protected from acid hydrolases by oligosaccharide sites that are either not recognized by lysosomal enzymes or simply interfere with hydrolases to interact with them.

The function of lysosomes is the provision of intracellular digestion, i.e., the splitting of both exogenous and endogenous substances.

Classification of lysosomes: primary lysosomes - electron-dense corpuscles; - secondary lysosomes - phagolysosomes, including autophagolysosomes; and tertiary lysosomes, or residual corpuscles.

Lysosomes

True lysosomes are small electron-dense corpuscles formed in the lamellar complex.

Dr. Nikonov
Dr. Nikonov

The article “The pathogenesis of cerebral palsy from my point of view, confirmed by the discoveries of the Nobel laureates” is of introductory nature.

 

The viewpoint of Nikolai Borisovich Nikonov, i.e. my point of view, may not coincide with the point of view of doctors of the World Health Organization, as well as experienced rehabilitation therapists practicing in rehabilitation centers.

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