Rad23A Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
--- [@rad2018] title: RAD23A Protein [@rada2020] --- [@xpcrad2017]
Rad23A Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
--- [@rad2018] title: RAD23A Protein [@rada2020] --- [@xpcrad2017]
:: infobox .infobox-protein [@rada2019] ::
Overview
RAD23 Homolog A (RAD23A) is a bifunctional protein involved in both nucleotide excision repair (NER) and the [ubiquitin-proteasome system](/mechanisms/ubiquitin-proteasome-system). It serves as a molecular adaptor that bridges DNA damage recognition proteins with the NER machinery and delivers polyubiquitinated substrates to the proteasome for degradation. RAD23A is highly expressed in neuronal tissues, where its dual roles in DNA repair and protein quality control are particularly important for maintaining neuronal health.
Structure
RAD23A is a 362-amino acid protein with multiple functional domains. It contains an N-terminal ubiquitin-like (Ubl) domain that interacts with the proteasome, and two C-terminal ubiquitin-binding (UBA) domains that bind polyubiquitinated proteins. RAD23A also has an XPC-binding domain that recruits it to DNA damage sites.
Normal Function
RAD23A has dual functions in nucleotide excision repair (NER) and the ubiquitin-proteasome system. As an XPC cofactor, RAD23A helps recruit the TFIIH complex to DNA damage sites for NER. As a proteasome-interacting protein, it helps deliver ubiquitinated substrates for degradation.
In [neurons](/entities/neurons), RAD23A's roles in DNA repair and protein quality control are both critical. Neuronal protein aggregates and DNA damage accumulate with age, potentially overwhelming these systems.
Role in Disease
Alzheimer's Disease
RAD23A helps clear damaged proteins via the proteasome. Impaired function may contribute to [amyloid-beta](/proteins/amyloid-beta) and [tau](/proteins/tau) aggregation in AD.
Parkinson's Disease
RAD23A-mediated protein quality control may be relevant to [alpha-synuclein](/proteins/alpha-synuclein) clearance. Impaired proteasome function is a feature of PD pathogenesis.
Therapeutic Targeting
No RAD23A-targeted therapies exist. Enhancing proteasome function is a therapeutic strategy being explored for neurodegenerative diseases.
Key Publications
[RAD23A structure and function in NER (2002)](https://doi.org/10.1016/s0092-8674(02)00710-9)
[RAD23 proteins in DNA repair (2018)](https://pubmed.ncbi.nlm.nih.gov/29446774/)
[RAD23A in proteasomal degradation (2020)](https://pubmed.ncbi.nlm.nih.gov/32845567/)
[XPC-RAD23 complex in damage recognition (2017)](https://pubmed.ncbi.nlm.nih.gov/29150379/)
[RAD23A in protein quality control (2019)](https://pubmed.ncbi.nlm.nih.gov/31141792/)
[DNA repair defects in AD (2019)](https://doi.org/10.1016/j.neurobiolaging.2019.06.012)
[RAD23 and neurodegeneration (2021)](https://pubmed.ncbi.nlm.nih.gov/33547680/)
[Therapeutic targeting of DNA repair (2022)](https://pubmed.ncbi.nlm.nih.gov/35608644/)
Background
The study of Rad23A Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
External Links
[PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
[Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
[Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data