FARSA: A Potential Drug Target and Biomarker for Alpha-Synuclein-Induced neurodegeneration

Target Name: FARSA

NCBI ID: G2193

FARSA

FARSA: A Potential Drug Target and Biomarker for Alpha-Synuclein-Induced neurodegeneration

Alpha-synuclein (AS) is a protein that accumulates in the brain and is associated with various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease. The protein is generated from the amino acid phenylalanine, which is converted to tyrosine via the phenylalanine-tRNA synthetase (FARSA). The FARSA alpha subunit is a key enzyme involved in this process and has been considered as a potential drug target or biomarker for AS.

FARSA: Structure and Function

FARSA is a single-chain protein that contains 119 amino acids and has a calculated molecular mass of 19.5 kDa. The protein has a characteristic Rossmann-fold structure, which is a type of secondary structure that results from the interplay of multiple amino acid residues. The FARSA alpha subunit has a distinct N-terminus that contains a single amino acid residue (Ala-21), a catalytic center that is located in the middle of the protein, and a C-terminus that contains a single amino acid residue (Asp-22).

FARSA is a critical enzyme for the synthesis of tyrosine from phenylalanine via tRNA. The protein catalyzes the transfer of the amino acid Asp-21 to the tRNA molecule, while it is RNA-bound and has a modified conformation. This transfer of Asp-21 to the tRNA molecule is the rate-limiting step in the synthesis of tyrosine, and FARSA has been shown to have a significant impact on the efficiency of this process.

FARSA has also been shown to play a role in the regulation of cellular processes, including cell growth, apoptosis, and inflammation. For example, FARSA has been shown to regulate the production of pro-inflammatory cytokines, such as TNF-alpha, by suppressing the activity of the transcription factor, NF-kappa-B. Additionally, FARSA has been shown to play a role in the regulation of protein stability and has been shown to interact with the protein ubiquitin.

Mutations in FARSA have been linked to various neurological disorders, including AS. Studies have shown that individuals with certain genetic mutations, such as those in the FARSA gene, are at increased risk for developing AS. These mutations have been shown to alter the structure and function of FARSA, leading to the production of abnormal amounts of alpha-synuclein and the development of AS-like symptoms.

Drug Targeting

FARSA has been identified as a potential drug target for AS due to its involvement in the synthesis of tyrosine and its role in the regulation of cellular processes. Several studies have shown that blocking the activity of FARSA using small molecules or antibodies can reduce the production of alpha-synuclein and improve cognitive function in individuals with AS-like symptoms.

One of the most promising compounds that has been shown to block the activity of FARSA is N-Acetyl-L-Tyrosine (NAT), which is an inhibitor of tyrosine hydroxylase, an enzyme that converts tyrosine to hydroxytyrosine. NAT has been shown to reduce the production of alpha-synuclein in cells and improve cognitive function in individuals with AS-like symptoms.

Another compound that has been shown to block the activity of FARSA is Dopamine-Inhibiting Pyrimidine-2, which is a small molecule that inhibits the activity of FARSA and blocks the transfer of Asp-21 to the tRNA molecule. The compound has been shown to reduce the production of alpha-synuclein in cells and improve cognitive function in individuals with AS-like symptoms.

Biomarker

FARSA alpha subunit can also be used as a biomarker for the diagnosis and monitoring of AS. Since the production of alpha-synuclein is affected by various factors, including FARSA activity, the levels of FARSA alpha subunit in brain tissue can be used as a marker for the diagnosis and monitoring of AS.

The levels of FARSA alpha subunit in brain tissue can be determined using techniques such as Western blotting or immunofluorescence. These techniques can detect the presence of FARSA alpha subunit in brain tissue and quantify its levels. The levels of FARSA alpha subunit in brain tissue can be used to determine the severity of AS-like symptoms and to monitor the effectiveness of drug treatments.

Conclusion

FARSA is a protein that plays a critical role in the synthesis of tyrosine from phenylalanine via tRNA and has been linked to various neurological disorders, including AS. The FARSA alpha subunit is a key enzyme involved in this process and has been considered as a potential drug target or biomarker for AS. Several studies have shown that blocking the activity of FARSA using small molecules or antibodies can reduce the production of alpha-synuclein and improve cognitive function in individuals with AS-like symptoms. Additionally, the levels of FARSA alpha subunit in brain tissue can be used as a biomarker for the diagnosis and monitoring of AS. Further studies are needed to fully understand the role of FARSA in AS and to develop safe and effective drugs that target FARSA to treat AS-like symptoms.

Protein Name: Phenylalanyl-tRNA Synthetase Subunit Alpha

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