HDAC6 Protein is a protein involved in key cellular signaling pathways relevant to neurodegenerative diseases. This page provides comprehensive information about its structure, normal biological function, and role in disease pathogenesis.
HDAC6 Protein participates in critical cellular processes that, when dysregulated, contribute to neurodegeneration. Understanding this protein's function is essential for developing therapeutic interventions for Alzheimer's disease, Parkinson's disease, and related conditions.
| HDAC6 Protein | |
|---|---|
| Protein Name | HDAC6 |
| Gene | [HDAC6](/genes/hdac6) |
| UniProt ID | Q9UQT8 |
| PDB Structure | 3C0K, 5W8V, 5EDU |
| Molecular Weight | 131 kDa |
| Subcellular Localization | Primarily cytoplasm, enriched in dendritic processes |
| Protein Family | Class IIb histone deacetylases |
HDAC6 is a unique class IIb HDAC primarily located in the cytoplasm. It contains two catalytic domains and a zinc-finger ubiquitin-binding domain (ZnF-UBP). The catalytic domains are functionally distinct. The ZnF-UBP domain binds ubiquitinated proteins, targeting them for autophagic degradation. HDAC6 lacks a functional NLS and is predominantly cytoplasmic.
HDAC6 is primarily a cytoplasmic deacetylase that regulates non-histone substrates including alpha-tubulin, Hsp90, and cortactin. It is a key regulator of protein quality control through autophagy and the aggresome pathway. HDAC6 recognizes ubiquitinated proteins and targets them for autophagic degradation. It also regulates molecular chaperone function, cell adhesion, and migration. In neurons, HDAC6 regulates synaptic plasticity and axonal transport.
HDAC6 is a promising therapeutic target for neurodegenerative diseases. In AD, HDAC6 inhibition reduces tau pathology and improves cognitive function in mouse models. HDAC6 regulates autophagy of misfolded proteins including tau and alpha-synuclein. In PD, HDAC6 protects against alpha-synuclein toxicity and mitochondrial dysfunction.
HDAC6 inhibitors are in advanced development. Tubastatin A and ACY-1215 (Ricolinostat) show benefits in AD and PD models. These inhibitors promote autophagy and improve clearance of pathological proteins. Several HDAC6 inhibitors have entered clinical trials for cancer and are being evaluated for neurodegenerative diseases.