Disorders Linked to Casein Kinase I Delta Mutation
Casein kinase I delta (CKIδ) mutations have been primarily linked to neurodegenerative disorders including Parkinson's disease, Alzheimer's disease, and sleep disorders, as well as certain types of cancer.
Neurological Disorders
Parkinson's Disease
- CKIδ mutations have been associated with Parkinson's disease pathogenesis 1
- CKIδ dysfunction contributes to hyperphosphorylation of key proteins implicated in Parkinson's disease development 2
- The kinase plays a role in cellular processes that, when disrupted, can lead to neurodegeneration
Alzheimer's Disease
- CKIδ has been linked to Alzheimer's disease through its role in protein hyperphosphorylation 2
- Aberrant activity of CKIδ contributes to pathological processes in Alzheimer's disease
Sleep Disorders
- CKIδ is involved in circadian rhythm regulation 3, 2
- Mutations affecting this function can lead to disruptions in sleep-wake cycles and circadian rhythm disorders
Amyotrophic Lateral Sclerosis (ALS)
- CKIδ dysfunction has been connected to ALS through protein hyperphosphorylation mechanisms 2
Cancer-Related Disorders
Triple Negative Breast Cancer
- CKIδ is amplified in approximately 30% of triple negative breast cancers 4
- High expression is observed in primary tumor cells and in tumor cells invading lymphatic nodes
- Plays a role in cancer cell proliferation, invasion, and migration
Choriocarcinoma
- Strong expression of CKIδ has been observed in choriocarcinomas 5
- Inhibition of CKIδ in trophoblast cells leads to apoptosis, suggesting its importance in cell survival
Other Cancers
- CKIδ is involved in various cellular processes including cell cycle progression, chromosome segregation, and cellular differentiation that are relevant to cancer development 3
- Deregulation of CKIδ expression and activity has been linked to proliferative diseases including various cancers
Molecular Mechanisms
CKIδ mutations affect multiple cellular processes:
- Cell cycle progression and mitotic spindle formation 5
- DNA damage repair mechanisms 2
- Apoptotic pathways 3, 5
- Cellular differentiation 3
- Protein phosphorylation, particularly of proteins involved in neurodegenerative processes 2
Clinical Implications
- CKIδ inhibitors are being developed as potential therapeutic agents for neurodegenerative disorders 2
- In cancer, particularly triple negative breast cancer, CKIδ inhibition shows promise in reducing proliferation, migration, and metastasis 4
- Understanding CKIδ's role in disease pathogenesis may lead to novel targeted therapies for both neurodegenerative disorders and certain cancers
The identification of CKIδ as a contributor to these disorders has opened new avenues for therapeutic intervention, with numerous inhibitors currently under development that may provide treatment options for conditions with limited current therapies.