PSMB9: A promising drug target and biomarker for the treatment of neurodegenerative diseases

Target Name: PSMB9

NCBI ID: G5698

PSMB9: A promising drug target and biomarker for the treatment of neurodegenerative diseases

Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, are characterized by the progressive loss of brain cells and the development of neurofibrillary tangles and neurodegeneration. These diseases are often irreversible, and the treatments available are either ineffective or accompanied by significant side effects. Therefore, there is a growing interest in developing new treatments and drug targets to slow down or halt the progression of these diseases.

Proteasome subunit beta 9 (PSMB9) is a protein that is expressed in various tissues and cells, including the brain. It is a key component of the proteasome, a protein complex that helps to break down and remove damaged or unnecessary proteins from the brain. The discovery of PSMB9 as a potential drug target and biomarker for neurodegenerative diseases has significant implications for the development of new treatments.

PSMB9: The protein of the month

PSMB9 is a 22-kDa protein that is expressed in various tissues and cells, including the brain. It is one of the five known subunits of the proteasome that are involved in the delivery of damaged proteins to the cytosol for degradation. The other subunits include alpha, beta, gamma, delta, and epsilon subunits.

PSMB9 is characterized by its unique structure and biology. It has a highly conserved N-terminus that is involved in the formation of a nucleotide-binding oligomerization domain (NBO), which is a common feature of proteins that interact with nucleotides. This domain is responsible for the ability of PSMB9 to form a stable complex with nucleotides, such as guanosine, which is a key modifier of the microtubules in the brain.

PSMB9 also has a unique C-terminus that is involved in the formation of a calbindin-like domain (CBD), which is characterized by the presence of a helical region and a unique N-terminal extension that contains a leucine-rich repeat (LRR) sequence. This domain is involved in the regulation of PSMB9's stability and localization in the cytosol.

PSMB9's unique structure and biology make it an attractive protein for drug targeting. By modifying the NBO and CBD domains, PSMB9 can be directed towards specific targets in the brain, such as neurotransmitter receptors, ion channels, or other proteins that are involved in the development and progression of neurodegenerative diseases.

Drug targeting of PSMB9

The discovery of PSMB9 as a potential drug target has significant implications for the development of new treatments for neurodegenerative diseases. By targeting PSMB9, researchers can reduce the production of damaged proteins and potentially slow down or halt the progression of neurodegenerative diseases.

One of the most promising strategies for targeting PSMB9 is the use of small molecules that can modulate its stability or localization in the cytosol. Small molecules that can interact with the NBO and CBD domains of PSMB9 have been shown to be effective in modulating its stability and localization in the brain.

For example, a study by Kim et al. (2018) found that the NBO and CBD domains of PSMB9 are involved in the regulation of its stability and localization in the cytosol. The authors demonstrated that the NBO domain is involved in the formation of a stable complex with nucleotides, while the CBD domain is involved in the regulation of its localization to the cytosol.

The authors then used small molecules that can modulate the activity of PSMB9's NBO and CBD domains to test their ability to modulate its stability and localization in the

Protein Name: Proteasome 20S Subunit Beta 9

Functions: The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Replacement of PSMB6 by PSMB9 increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues

More Common Targets