Ibrain protein phosphorylation: a potential target for glioma development

Glioma is one of the most common primary brain tumors, and the mortality rate of the disease is second only to cardiovascular and cerebrovascular diseases
.
It is difficult to eradicate with conventional surgery, and it often recurs and increases its malignancy and eventually leads to death
.
Studying the pathogenesis of glioma and exploring effective treatments is one of
the most important topics at present.
Based on histopathology and clinical features, gliomas are classified into four grades (I, II, III, IV).

Grade I is benign glioma, grade II is between the benign and malignant boundaries of glioma, and grade III and above are malignant gliomas
.
Gliomas are also divided into oligodendroglioma, astrocytoma, medulloblastoma, glioblastoma (GBM), ependymoma, and choroid plexus papilloma
.
GBM is the most common one, it is a grade IV astrocytoma whose aggressive nature leads to a relatively high mortality rate
.
Malignant gliomas grow rapidly and cause more severe cerebral edema, and although temozolomide chemotherapy increases long-term survival, treatment failure and rapid recurrence of gliomas remain common
.
In addition, despite a combination of surgery, radiotherapy, and chemotherapy, low-grade gliomas mechanically deregulate diseased areas from normal brain regions
.
Patients with high-grade gliomas have a shorter survival time, with an average survival of less than 1 year
.

Protein phosphorylation is necessary for the initiation of many biological phenomena, including cell growth, proliferation, apoptosis, etc.
, phosphorylation can directly regulate all aspects of protein function, strictly regulated by protein phosphatase and protein kinase, once protein phosphorylation regulation is abnormal, often lead to serious diseases, such as cancer, glioma, etc
.
Therefore, protein phosphorylation plays a leading role in various activities of glioma and can also be used as a target to regulate the development of glioma
.
Altering the phosphorylation of any one protein may be associated with gliomas, and they can serve as potential targets for drug development to treat
gliomas.
Thus, drugs that target phosphorylation pathways represent a promising area
for glioma treatment.

Fig.
1 Phosphorylation affects the protein interaction network of regulatory proteins related to glioma growth, proliferation, invasion, apoptosis and autophagy

Currently, many drug studies involve protein phosphorylation
.
Similarly, various treatments for glioma are related to
protein phosphorylation.
Studies have found that GALNT2 is inseparable
from the physiological processes of glioma cell proliferation, migration and invasion.
However, the mechanism by which GALNT2 promotes the malignant characteristics of glioma is to inhibit the phosphorylation of Akt, FAK and zyxin by inhibiting EGFR phosphorylation while inhibiting p110β and JNK, thereby inhibiting the proliferation and migration
of GBM cells.
In addition, histone phosphorylation plays an important regulatory role
in DNA repair structure and transcription during cell proliferation and apoptosis.
STAT3 phosphorylation can regulate the physiological processes of glioma proliferation, migration, invasion, apoptosis and so STAT is a good regulatory target, and the inhibition of glioma through STAT phosphorylation has a good therapeutic prospect.

AKT and FGFR have also become important therapeutic targets for gliomas, and they can play an active role
in the treatment of gliomas by improving the sensitivity of glioma by targeting phosphorylation.
Phosphorylation of many proteins can affect the development of
gliomas.
In summary, protein phosphorylation will be a breakthrough and provide new ideas
for the treatment of gliomas.

Fig.
2 Mechanism structure of phosphorylation acting on glioma

The aim of this review was to investigate the effects of protein phosphorylation on gliomas, understand its pathological mechanisms, and analyze
them in depth.
Protein phosphorylation is associated with glioma cell genesis, growth, proliferation, migration, invasion, resistance, and death, while other properties of glioma cells need to be further studied
.
As we all know, phosphorylation and dephosphorylation of proteins is a reversible process, which regulates the development of the cytoskeleton and the proliferation, differentiation, apoptosis, and all processes
of life activities.
Reversible protein phosphorylation is one of
the major signal transduction modes known.
Therefore, glioma cells
can be effectively controlled by protein phosphorylation.
Although the targeted therapy of intracellular signaling pathways has not yet achieved very satisfactory results, we believe that the targeted regulation of protein phosphorylation can achieve great results in the future, and its targeted drugs can be further developed and put into clinical use, providing another way
for patient treatment.

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https://onlinelibrary.
wiley.
com/doi/10.
1002/ibra.
12038

Quote from the original

Pi, Y,  Fang, C-L,  Su, Z-Y.
 Protein phosphorylation: a potential target in glioma development.
ibrain.
 2022; 8: 176- 189.
doi:10.
1002/ibra.
12038

About Ibrain

Ibrain is an English-language open access journal
in the field of neuroscience published by Wiley, a global leader in research and education, and sponsored by the Affiliated Hospital of Zunyi Medical University.
The journal publishes cutting-edge research on the brain, spinal cord and nerves, providing neuroscientists with a platform
for communication in basic and translational medicine as well as clinical practice.
Ibrain is edited by Professor Wang Tinghua, Director of the Department of Neurological Diseases, West China Hospital, Sichuan University, and Professor Xin-Fu Zhou
, University of South Australia.

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Ibrain is interested in topics related to brain, spinal cord, and neurological diseases, including but not limited to clinical medicine, molecular diagnostics, epigenetics/genetics, cell biology, drug discovery, evolutionary medicine, nanotechnology, and artificial intelligence
.
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