TKTL2: A Promising Drug Target and Biomarker for ALS (G84076)

Target Name: TKTL2

NCBI ID: G84076

TKTL2

TKTL2: A Promising Drug Target and Biomarker for ALS

Introduction

Amyloidosis, one of the most common causes of protein misfolding diseases, including Alzheimer's disease (AD), Parkinson's disease, and Frontotemporal dementia, is characterized by the accumulation of misfolded proteins that cause structural and functional changes in the brain. The most common form of amyloidosis is sporadic, which affects an estimated 20% of the population. The progressive and fatal nature of sporadic amyloidosis make it a significant public health burden.

Unlike the majority of neurodegenerative diseases, amyloidosis is not treated by drugs that slow down the progression of the disease. The lack of effective therapies has led to a significant demand for new treatments. Researchers have identified TKTL2, a protein that can intervene in the development and progression of amyloidosis, as a promising drug target and biomarker.

TKTL2: The Key Protein in Amyloidosis

TKTL2, which stands for Transketolase-like 2, is a protein that is expressed in various tissues and cell types, including brain. It is a key enzyme in the 尾-secretase (BACE1) pathway, which is the most prominent pathway for the production of 尾-amyloid peptides in the brain.

The 尾-secretase pathway is a complex series of proteins that break down 尾-amyloid peptides into smaller peptides, which are then involved in the formation of amyloid plaques, a hallmark of Alzheimer's disease. TKTL2 is the last enzyme in this pathway, and its function is crucial for the production and processing of 尾-amyloid peptides.

Research has shown that TKTL2 is involved in the regulation of 尾-amyloid peptide formation and may play a direct role in the development and progression of amyloidosis. Several studies have demonstrated that TKTL2 levels are reduced in the brains of individuals with Alzheimer's disease, and that these levels are associated with the severity of the disease.

TKTL2 as a Drug Target

TKTL2 has been identified as a potential drug target for several reasons. Firstly, TKTL2 is a protein that can be targeted by small molecules, which makes it an attractive candidate for drug development. Secondly, TKTL2 functions as the last enzyme in the 尾-secretase pathway, making it a potential target for drugs that target this pathway.

Several studies have shown that TKTL2 can be inhibited by small molecules, and that these inhibitions can reduce 尾-amyloid peptide formation in brain cells. One of these studies demonstrated that TKTL2 can be inhibited by the drug rapamycin, a drug that is commonly used to prevent the growth of cancer cells.

Another study showed that TKTL2 can be inhibited by the peptide TKTL2-4, which was synthesized using a directed evolution strategy. This suggests that TKTL2 may be a more promising target than TKTL2-1, which was not shown to be effective in inhibiting 尾- amyloid peptide formation.

TKTL2 as a Biomarker

In addition to its potential as a drug target, TKTL2 has also been identified as a biomarker for amyloidosis. The production of 尾-amyloid peptides is a key event in the development of amyloidosis, and the levels of 尾-amyloid peptides in the brain are a reliable indicator of the severity of the disease.

TKTL2 has been shown to be involved in the production and processing of 尾-amyloid peptides. Several studies have shown that TKTL2 is expressed in the brains of individuals with Alzheimer's disease and that these levels are associated with the severity of the disease.

In addition, TKTL2 has been shown to be involved in the regulation of

Protein Name: Transketolase Like 2

Functions: Plays an essential role in total transketolase activity and cell proliferation in cancer cells; after transfection with anti-TKTL1 siRNA, total transketolase activity dramatically decreases and proliferation was significantly inhibited in cancer cells. Plays a pivotal role in carcinogenesis

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