Cyclin D1 (CCND1) is a regulatory subunit of cyclin-dependent kinases (CDKs) that controls the G1/S phase transition of the cell cycle. While primarily studied in cancer biology, Cyclin D1 has emerged as an important player in neuronal cell cycle dysregulation observed in neurodegenerative diseases.
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| Gene | [CCND1](/genes/ccnd1) |
|---|
| UniProt ID | P24385 |
|---|
| PDB ID | 3MRD, 5EX4 |
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| Protein Family | Cyclin family |
|---|
| Molecular Weight | ~34 kDa |
|---|
| Subcellular Localization | Nucleus, Cytoplasm |
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| Expression | Proliferating cells; low in mature [neurons](/entities/neurons) |
|---|
Cyclin D1 possesses the canonical cyclin fold structure:
- N-terminal region: Required for CDK binding and activation
- Cyclin box domain: Conserved 100 amino acid sequence that binds CDKs (especially CDK4 and CDK6)
- C-terminal region: Contains degron sequences for protein turnover
- PEST sequences: Rich in proline, glutamic acid, serine, threonine
In the normal nervous system:
- Cell cycle control: Regulates G1/S transition in dividing neural progenitor cells
- Development: Essential during neurogenesis
- Oligodendrocyte proliferation: Controls oligodendrocyte precursor cell division
- Synaptic plasticity: May modulate synaptic remodeling
In mature neurons, CCND1 expression is typically very low as these cells are post-mitotic.
In AD, Cyclin D1 dysregulation is prominent:
- Re-expression in AD neurons: Aberrant cell cycle entry in vulnerable neurons [1]
- Tau phosphorylation: Interaction with CDK4/6 promotes tau pathology [2]
- Aβ-induced toxicity: Contributes to neuronal dysfunction [3]
- Correlates with neurofibrillary tangle burden [4]
In PD:
- Elevated in dopaminergic neurons
- Associated with alpha-synuclein pathology
- Contributes to mitochondrial dysfunction
- May drive neuronal senescence [5]
In ALS:
- Dysregulated in motor neurons
- Associated with TDP-43 pathology
- Contributes to cell cycle re-entry
- May exacerbate proteostasis failure [6]
In HD:
- Increased Cyclin D1 in medium spiny neurons
- Contributes to transcriptional dysregulation
- May interact with mutant huntingtin
- Linked to striatal neuron vulnerability [7]
- CDK4/6 inhibitors (e.g., palbociclib): Indirectly modulate Cyclin D1 activity
- Gene expression modulators: Downregulate CCND1 transcription
- Cell cycle normalization: Restore post-mitotic state in neurons
- CDK4/6 inhibitors approved for cancer, being repurposed
- Preclinical studies show promise in neurodegeneration models
- Clinical trials for AD underway
| Partner |
Interaction Type |
Function |
| CDK4 |
Binding |
Kinase complex formation |
| CDK6 |
Binding |
Kinase complex formation |
| p21/CDKN1A |
Regulation |
CDK inhibition |
| p27/CDKN1B |
Regulation |
CDK inhibition |
| RB1 |
Phosphorylation |
Cell cycle progression |
| RbAp46/48 |
Chromatin remodeling |
Transcriptional control |