### PSMD8 Gene Overview

**Gene Symbol:** PSMD8  
**Location:** Chromosome 17

**Description:**  
The PSMD8 gene encodes a non-ATPase regulatory subunit of the 26S proteasome, which is critical for the degradation of ubiquitinated proteins. This process is essential for maintaining cellular protein homeostasis, regulating various cellular processes, and responding to cellular stresses. This particular subunit is part of the 19S regulatory complex, which helps in recognizing and unfolding substrates for degradation by the 20S core.

### 1. Associated Genes
The PSMD8 gene is associated with other genes that are involved in proteasome function and ubiquitin-mediated protein degradation. Notable associated genes include:
- **PSMC2** (Proteasome 26S subunit ATPase 2) - A part of the ATPase complex of the 19S regulator.
- **PSMD2** - Another non-ATPase subunit of the 19S regulator.
- **USP14** (Ubiquitin specific peptidase 14) - An enzyme that interacts with the proteasome to enhance its activity by deubiquitinating substrates.
- **RPN8** - Another essential component of the 19S regulatory complex.

### 2. Aging and Age-Related Diseases
The PSMD8 gene has been implicated in various age-related diseases, primarily due to its role in the proteasome pathway. Dysregulation of protein degradation is linked to:
- **Neurodegenerative diseases** such as Alzheimer’s and Parkinson’s disease, where accumulation of misfolded proteins is a hallmark.
- **Cancer**, where proteasome activity can promote the degradation of tumor suppressors.
- **Muscle atrophy and sarcopenia**, which are partly driven by age-related declines in proteasome function, affecting muscle protein turnover and regeneration.

Moreover, studies have suggested that the efficiency of the proteasome, including components like PSMD8, declines with age, leading to increased cellular stress and senescence.

### 3. Drug Interactions
Several drugs and drug classes have been found to interact with the proteasome and its regulatory components, including PSMD8:
- **Proteasome inhibitors** such as Velcade (bortezomib) and Carfilzomib have gained prominence in treating multiple myeloma and other cancers. These drugs act by preventing the degradation of pro-apoptotic factors and cause apoptosis of malignant cells.
- **Histone deacetylase inhibitors (HDACis)** like Vorinostat, which can indirectly influence proteasome activity and degradation pathways.
- Potential emerging compounds targeting the ubiquitin-proteasome system (UPS) for therapeutic interventions in age-related diseases and cancer.

### 4. Pathways and Biological Processes
PSMD8 is involved in multiple biological pathways and processes, including but not limited to:
- **Proteasome-mediated protein catabolism:** This pathway is crucial for regulated degradation of proteins tagged with ubiquitin.
- **Regulation of cell cycle:** The proteasome plays a key role in cell cycle progression by regulating cyclin and cyclin-dependent kinase levels.
- **Apoptotic signaling:** By regulating the degradation of pro-apoptotic factors, PSMD8 contributes to apoptosis.
- **DNA repair mechanisms:** The proteasome is involved in the removal of damaged or modified proteins that may arise due to DNA damage.

In summary, PSMD8 is a vital component of the ubiquitin-proteasome pathway, influencing various cellular functions and having implications in aging, age-related diseases, and therapeutic interventions targeting these pathways.