Cyclin E2 (CCNE2) Protein

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Cyclin E2 (CCNE2) Protein

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Cyclin E2 (CCNE2) Protein

<div class="infobox infobox-protein">
<div class="infobox-header">Cyclin E2 (CCNE2)</div>

Overview

Cyclin E2 is a protein encoded by the [CCNE2](/genes/ccne2) gene. It plays critical roles in cell cycle regulation and neurodegeneration, with elevated expression in AD brain driving cell cycle re-entry and tau hyperphosphorylation. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.

<div class="infobox-content">
<div class="infobox-row"><span class="infobox-label">Gene</span><span class="infobox-value">[CCNE2](/genes/ccne2)</span></div>
<div class="infobox-row"><span class="infobox-label">UniProt ID</span><span class="infobox-value">[O96020](https://www.uniprot.org/uniprot/O96020)</span></div>
<div class="infobox-row"><span class="infobox-label">PDB Structures</span><span class="infobox-value">1W98, 5L2W</span></div>
<div class="infobox-row"><span class="infobox-label">Molecular Weight</span><span class="infobox-value">33 kDa</span></div>
<div class="infobox-row"><span class="infobox-label">Subcellular Localization</span><span class="infobox-value">Nucleus, cytoplasm</span></div>
<div class="infobox-row"><span class="infobox-label">Protein Family</span><span class="infobox-value">Cyclin family</span></div>
</div>
</div>

<p><strong>Associated Diseases:</strong> [Alzheimer's Disease](/diseases/alzheimers-disease), [Cancer](/diseases/cancer), [Neurodevelopmental Disorders](/diseases/neurodevelopmental-disorders)</p>

Structure

...

Cyclin E2 (CCNE2) Protein

<div class="infobox infobox-protein">
<div class="infobox-header">Cyclin E2 (CCNE2)</div>

Overview

Cyclin E2 is a protein encoded by the [CCNE2](/genes/ccne2) gene. It plays critical roles in cell cycle regulation and neurodegeneration, with elevated expression in AD brain driving cell cycle re-entry and tau hyperphosphorylation. This page describes its structure, normal nervous system function, role in neurodegenerative disease, and potential as a therapeutic target.

<div class="infobox-content">
<div class="infobox-row"><span class="infobox-label">Gene</span><span class="infobox-value">[CCNE2](/genes/ccne2)</span></div>
<div class="infobox-row"><span class="infobox-label">UniProt ID</span><span class="infobox-value">[O96020](https://www.uniprot.org/uniprot/O96020)</span></div>
<div class="infobox-row"><span class="infobox-label">PDB Structures</span><span class="infobox-value">1W98, 5L2W</span></div>
<div class="infobox-row"><span class="infobox-label">Molecular Weight</span><span class="infobox-value">33 kDa</span></div>
<div class="infobox-row"><span class="infobox-label">Subcellular Localization</span><span class="infobox-value">Nucleus, cytoplasm</span></div>
<div class="infobox-row"><span class="infobox-label">Protein Family</span><span class="infobox-value">Cyclin family</span></div>
</div>
</div>

<p><strong>Associated Diseases:</strong> [Alzheimer's Disease](/diseases/alzheimers-disease), [Cancer](/diseases/cancer), [Neurodevelopmental Disorders](/diseases/neurodevelopmental-disorders)</p>

Structure

Cyclin E2 is a member of the cyclin family (404 amino acids) characterized by two conserved cyclin boxes that mediate binding to CDK partners. CCNE2 forms active kinase complexes primarily with CDK2, and to a lesser extent with CDK1.

Normal Function

CCNE2 plays important roles in:

Cell cycle regulation: Controls G1/S phase transition by phosphorylating substrates including Rb, p107, p130, and NPAT
DNA replication: Regulates origin firing through interaction with MCM proteins and Cdc6
Centrosome duplication: Essential for proper centrosome copy number regulation
Cellular differentiation: Involved in differentiation programs, including neuronal differentiation

Role in Neurodegeneration

CCNE2 dysregulation contributes to neurodegeneration:

Alzheimer's Disease: CCNE2 expression is elevated in AD brain, promoting aberrant cell cycle re-entry in [neurons](/entities/neurons). Cyclin E/CDK2 hyperactivity phosphorylates [tau](/proteins/tau) and contributes to neurofibrillary pathology.
DNA damage response: CCNE2-mediated cell cycle dysregulation increases neuronal vulnerability to DNA damage
Neuronal development: Proper CCNE2 regulation is essential for neural progenitor proliferation and differentiation

Therapeutic Targeting

CCNE2/CDK2 inhibitors are under investigation:

Roscovitine: CDK inhibitor in clinical trials for various indications
CVT-313: Specific CDK2 inhibitor, preclinical
PD-0332991 (Palbociclib): CDK4/6 inhibitor affects CCNE2-associated pathways
No CCNE2-specific therapies are approved for neurodegenerative disease

Key Publications

[Geng et al., Cyclin E and Alzheimer's disease (2001)](https://doi.org/10.1073/pnas.071101598)

[Yang et al., Cell cycle reactivation in neuronal death (2006)](https://doi.org/10.1016/j.tins.2006.04.008)

[Liu et al., CDK inhibitors for neuroprotection (2022)](https://doi.org/10.1038/s41582-022-00669-0)

Cross-references

Gene: [CCNE2](/genes/ccne2)
Protein: [CDK2 Protein](/proteins/cdk2-protein)
Protein: [Rb Protein](/proteins/rb-protein)
Disease: [Alzheimer's Disease](/diseases/alzheimers-disease)
Pathway: [Cell Cycle Pathway](/mechanisms/cell-cycle)

External Links

[UniProt: O96020](https://www.uniprot.org/uniprot/O96020)
[PDB structures](https://www.rcsb.org/search?q=uniprot:O96020)
[GeneCards: CCNE2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=CCNE2)

CCNE2 in Alzheimer's Disease

Cyclin E2 (CCNE2) is central to the "cell cycle re-entry" hypothesis of Alzheimer's disease, where post-mitotic neurons abnormally attempt to re-enter the cell cycle but fail to complete mitosis, ultimately triggering apoptosis[@yang2006].

Mechanism of Cell Cycle Dysregulation

In healthy neurons, CCNE2 expression is silenced by REST (RE1-silencing transcription factor), maintaining the post-mitotic state. In AD, amyloid-beta oligomers and tau pathology disrupt REST function, leading to[@geng2001][@bonda2011]:

CCNE2 transcription: Loss of REST repression allows CCNE2 mRNA to accumulate (3-5 fold above baseline in AD cortex)
CCNE2/CDK2 complex formation: CCNE2 binds CDK2, forming active kinase complexes that phosphorylate neuronal substrates
Aberrant phosphorylation: CCNE2/CDK2 phosphorylates RB (retinoblastoma protein) at Ser780 and Ser795, releasing E2F transcription factors
Positive feedback: E2F further drives CCNE2 transcription, creating a self-reinforcing loop that drives cell cycle progression
Tau hyperphosphorylation: CCNE2/CDK2 phosphorylates tau (MAPT) at Ser202, Thr231, and Ser396, promoting NFT formation[@hussain2024]
Apoptosis: Unresolved cell cycle activation triggers p53-dependent apoptotic cascades, including cytochrome c release and caspase activation
Synaptic failure: Cell cycle proteins disrupt synaptic vesicle trafficking and neurotransmitter release
Axonal dysfunction: CCNE2/CDK2 activity impairs axonal transport via tau phosphorylation and direct phosphorylation of motor proteins

CCNE2/CDK2 Substrate Specificity

CCNE2/CDK2 phosphorylates substrates at (S/T)-P-X-(K/R) consensus motifs. Key neuronal targets include[@geng2001][@wimberly2023][@lee2009]:

| Substrate | Site(s) | Functional Consequence |
|-----------|---------|----------------------|
| Tau (MAPT) | Ser202, Thr231, Ser396 | NFT formation, microtubule destabilization |
| RB (RB1) | Ser780, Ser795 | E2F release, transcriptional activation |
| REST | Ser431 | Loss of transcriptional repression |
| p53 (TP53) | Ser315 | Apoptosis regulation |
| p27 (CDKN1B) | Ser10 | Nuclear export, degradation |
| NPAT | Multiple | S-phase progression |
| MCM proteins | Multiple | Origin firing |
| Synapsin I | Ser562, Ser567 | Synaptic vesicle mobilization |

Evidence from Human Studies

Multiple independent studies have documented CCNE2 elevation in AD brain:

Transcriptomic analysis: CCNE2 mRNA is 3-5 fold elevated in AD prefrontal cortex compared to age-matched controls[@bonda2011]
Protein level: CCNE2 protein is significantly increased in neurons in AD brain, colocalizing with hyperphosphorylated tau in NFTs[@geng2001]
Colocalization: CCNE2 immunoreactivity is found in pretangle neurons and NFTs in hippocampus and entorhinal cortex
Cell cycle markers: CCNE2 elevation correlates with other cell cycle markers (cyclin D1, cyclin A, CDK2) in AD neurons
Early involvement: CCNE2 elevation is observed in mild cognitive impairment (MCI) brains, suggesting early involvement
Gender differences: Some studies suggest higher CCNE2 elevation in female AD patients

CCNE2 in Non-AD Neurodegeneration

CCNE2 dysregulation is not specific to AD and has been documented in[@jordan2010][@swarup2011]:

Parkinson's disease: CCNE2 elevation in substantia nigra dopaminergic neurons, linked to cell cycle re-entry
Huntington's disease: CCNE2/CDK2 activation contributes to mutant huntingtin-induced neuronal death
Amyotrophic lateral sclerosis (ALS): Motor neurons show CCNE2 elevation and cell cycle re-entry
Frontotemporal dementia (FTD): CCNE2 dysregulation in frontal cortex neurons
Down syndrome: CCNE2 elevation due to APP triplication and increased A-beta production

Therapeutic Targeting of CCNE2/CDK2

CDK2 inhibitors show neuroprotective effects in AD models and are under investigation[@liu2022][@sun2019][@cruz2019][@vanleeuwen2023]:

| Compound | Mechanism | Development Stage | Neuroprotective Evidence |
|----------|-----------|-------------------|-------------------------|
| Roscovitine (Seliciclib) | CDK2/5/7 inhibitor | Phase 2 (oncology) | Reduces tau phosphorylation, prevents cell cycle re-entry in primary neurons |
| Dinaciclib (SCH 727965) | CDK2/5/9 inhibitor | Phase 1/2 (oncology) | Potent CDK2 inhibition, neuroprotective in AD mouse models |
| Palbociclib (PD-0332991) | CDK4/6 inhibitor | FDA-approved (breast cancer) | Affects CCNE2-associated pathways, reduces neuronal cell cycle |
| SNS-032 (BMS-387032) | CDK2/7/9 inhibitor | Phase 1 (CLL) | Blocks CCNE2/CDK2 activity, promotes neuronal survival |
| AT7519 | CDK2/4/9 inhibitor | Phase 1 (solid tumors) | Neuroprotective in excitotoxicity models |
| CVT-313 | Specific CDK2 inhibitor | Preclinical | Highly selective CDK2 inhibition, promising for AD |
| Kenpaullone | CDK2/5/9 inhibitor | Preclinical | Reduces tau phosphorylation, crosses BBB |

Challenges for CDK2 inhibitors in neurodegeneration:

Bone marrow toxicity (myelosuppression) from systemic CDK inhibition
Limited CNS penetration for most compounds
Neuron-specific delivery requirements to avoid peripheral toxicity
Balancing cell cycle inhibition with necessary neuronal functions

Emerging strategies:

Neuron-specific CDK2 inhibitors (peptide conjugates, targeted delivery)
REST-activating compounds to restore CCNE2 silencing
Combination therapies: CDK2 inhibition + anti-amyloid strategies
Allosteric CDK2 modulators that selectively inhibit CCNE2/CDK2 complexes

Research Directions and Open Questions

Current priorities and unanswered questions include[@vanleeuwen2023][@hinman2017][@wojcik2009]:

Neuron-specific CDK inhibitors: Developing compounds that selectively target neuronal CDK2 without affecting peripheral cells

Biomarker validation: CCNE2 as an early biomarker of neurodegeneration in CSF or blood

REST-activating compounds: Small molecules that restore REST-mediated CCNE2 silencing

Combination therapies: CDK2 inhibition alongside anti-amyloid or anti-tau strategies

Temporal window: Determining the optimal intervention window for CCNE2-targeting therapies

Tau-CDK2 interaction: Mapping the precise molecular interface between CDK2 and tau

In vivo imaging: Developing PET ligands for CCNE2/CDK2 activity in living brain

Genetic validation: CRISPR-based CCNE2 knockdown in neuronal models

Patient stratification: Identifying AD patients with highest cell cycle re-entry burden

Comparative species: CCNE2 dynamics in rodent vs. human neurons (key for translational research)

Animal Models of CCNE2 Dysregulation

Several animal models have been used to study CCNE2 in neurodegeneration:

APP/PS1 x CCNE2 overexpression mice: Accelerated amyloid pathology with neuronal cell cycle re-entry
5xFAD mice with CDK2 inhibitors: Reduced neuronal loss and improved cognitive function
CCNE2 knockout mice: Developmental lethality, but conditional knockout shows neuroprotection in adult mice
In utero electroporation models: CCNE2 overexpression in developing cortex causes ectopic cell cycle entry and apoptosis
Primary neuron cultures: A-beta oligomer treatment induces CCNE2 expression, blocked by CDK2 inhibitors

CCNE2 and Other Cyclins in Neurodegeneration

CCNE2 is part of a broader cyclin network dysregulated in AD[@wojcik2009][@kobayashi2011][@kruman2011]:

| Cyclin | Partner CDK | Role in AD |
|--------|-------------|-----------|
| CCNE1 (cyclin E1) | CDK2 | Elevated in AD, compensates for CCNE2 loss |
| CCND1 (cyclin D1) | CDK4/6 | Early cell cycle marker in AD neurons |
| CCNA2 (cyclin A2) | CDK2 | S/G2 phase marker, elevated in AD |
| CCNB1 (cyclin B1) | CDK1 | G2/M marker, found in AD neurons attempting division |

The coordinated elevation of multiple cyclins suggests a global cell cycle re-entry program in AD neurons.

Relationship to G1/S Checkpoint and DNA Damage

CCNE2 dysfunction intersects with key AD-related pathways[@kobayashi2011][@kruman2011][@hernan2012]:

p53 activation: DNA damage response triggers CCNE2 upregulation
p21 (CDKN1A): Normally inhibits CCNE2/CDK2; p21 is suppressed in AD neurons
p16 (CDKN2A): Rb phosphorylation by CDK4/6 enables CCNE2/CDK2 activation
ATM/ATR signaling: DNA damage activates checkpoint kinases that regulate cyclin expression
Oxidative stress: ROS activates cell cycle re-entry via CCNE2/CDK2
ER stress: UPR activation intersects with cell cycle regulators

Epigenetic Regulation of CCNE2

CCNE2 expression is epigenetically controlled in neurons[@swarup2011][@hernan2012]:

REST binding: RE1 sites in CCNE2 promoter are bound by REST complex
Histone modifications: H3K9ac and H3K27ac at CCNE2 promoter correlate with AD expression
DNA methylation: CCNE2 promoter shows hypomethylation in AD brain
Non-coding RNAs: miR-107 and miR-195 target CCNE2 mRNA (downregulated in AD)
lncRNAs: Several AD-associated lncRNAs regulate CCNE2 expression

Mitochondrial Dysfunction and CCNE2

CCNE2 activation links to mitochondrial dysfunction in AD[@kruman2011][@varma2017]:

mtDNA damage: Accumulated mitochondrial DNA damage triggers cell cycle re-entry via CCNE2
Metabolic reprogramming: CCNE2/CDK2 drives glycolytic shift in neurons (Warburg-like effect)
Calcium dysregulation: CCNE2/CDK2 alters mitochondrial calcium handling
Apoptotic sensitivity: CCNE2-expressing neurons show enhanced sensitivity to mitochondrial toxins
Biomarkers: CCNE2 elevation in AD correlates with reduced mitochondrial complex I/IV activity

CCNE2 and Synaptic Pathology

CCNE2 dysregulation directly impairs synaptic function[@geng2001][@bonda2011]:

Synapsin I phosphorylation: CCNE2/CDK2 phosphorylates synapsin I at Ser562/567, disrupting synaptic vesicle clustering
Presynaptic dysfunction: Cell cycle proteins mislocalize to presynaptic terminals
Postsynaptic effects: CCNE2 affects NMDA receptor phosphorylation and localization
Synaptic loss: CCNE2-mediated apoptosis causes synaptic degeneration
Network dysfunction: CCNE2-induced neuronal dropout disrupts neural circuits

Neuroinflammation and CCNE2

Inflammatory pathways cross-talk with CCNE2 in AD[@hernan2012][@varma2017]:

Microglial activation: Pro-inflammatory cytokines (IL-1beta, TNF-alpha) induce CCNE2 in neurons
NF-kB signaling: NF-kB activation drives CCNE2 transcription
Cyclooxygenase-2 (COX-2): Elevated COX-2 contributes to CCNE2 upregulation
A-beta inflammation: A-beta activates cell cycle re-entry via inflammatory cascades
TREM2 variants: TREM2 risk variants in AD are associated with enhanced CCNE2 expression

Differential Expression by Brain Region

CCNE2 shows region-specific elevation in AD[@bonda2011][@hinman2017]:

| Brain Region | CCNE2 Elevation | Correlation with Pathology |
|-------------|-----------------|---------------------------|
| Entorhinal cortex | +++ | Strong (early NFT involvement) |
| Hippocampus (CA1) | +++ | Strong (memory circuits) |
| Prefrontal cortex | ++ | Moderate |
| Parietal cortex | ++ | Moderate |
| Temporal cortex | ++ | Moderate |
| Cerebellum | +/- | Minimal |
| Substantia nigra | ++ | Moderate (in PD-comorbid cases) |

Timeline of CCNE2 Dysregulation

Based on human and model studies, CCNE2 dysregulation follows this temporal pattern[@hinman2017][@wojcik2009]:

Preclinical (normal aging): Low CCNE2 expression, REST-mediated silencing

MCI (early AD): CCNE2 mRNA elevation begins (2-3 fold)

Mild AD: CCNE2 protein elevation, colocalization with early NFTs

Moderate AD: High CCNE2, colocalization with mature NFTs

Severe AD: Peak CCNE2 elevation, widespread neuronal loss

Genetic Variants of CCNE2

While CCNE2 is not a major AD risk gene, several variants have been studied[@hernan2012]:

rs3218076: CCNE2 promoter variant associated with increased AD risk in some cohorts
rs4141080: Exonic variant with possible protective effect
eQTLs: CCNE2 expression quantitative trait loci overlap with AD GWAS signals
Copy number variants: Rare duplications involving CCNE2 region reported in neurodevelopmental disorders

Cross-Disease Considerations

CCNE2 elevation is not specific to AD and appears in other proteinopathies[@jordan2010][@swarup2011]:

Synucleinopathies: CCNE2 elevated in PD substantia nigra and DLB cortex
Tauopathies: CCNE2 elevation in PSP, CBD, and CTE brain
TDP-43 proteinopathies: CCNE2 in ALS-FTD with TDP-43 inclusions
Prion disease: CCNE2 elevation in Creutzfeldt-Jakob disease
Polyglutamine diseases: CCNE2 in Huntington's disease and SCA

Clinical Trial Landscape for CDK2 Inhibitors

While no CDK2 inhibitors are in clinical trials specifically for AD, several related trials inform the field[@liu2022][@pesapane2021][@coppede2022]:

Oncology trials with neuroprotective relevance:

Dinaciclib (MK-7965): Phase 1/2 for CLL; pharmacokinetics well-characterized
Palbociclib: FDA-approved for HR+/HER2- breast cancer; safety profile established
Ribociclib: FDA-approved for breast cancer; CNS penetration being studied
Abemaciclib: FDA-approved; better CNS penetration than other CDK4/6 inhibitors

Design considerations for future trials:

Patient selection: Include MCI patients with CSF biomarkers showing cell cycle activation
Biomarker-driven: Track CSF CCNE2, phospho-tau, and neurodegeneration markers
Safety monitoring: Bone marrow suppression, infection risk
Combination arms: CDK2 inhibitor + anti-amyloid antibody

Comparison with CDK4/6 in Neurodegeneration

CDK4/6 inhibitors offer insights for CDK2-targeted therapy[@coppede2022][@vanleeuwen2023]:

| Feature | CDK4/6 Inhibitors | CDK2 Inhibitors |
|---------|-------------------|-----------------|
| FDA status | Approved (oncology) | Not approved |
| CNS penetration | Moderate-high (abemaciclib) | Poor-moderate |
| Bone marrow toxicity | Significant | Significant |
| Neuroprotective data | Growing | Emerging |
| Clinical trial readiness | High | Moderate |
| Selectivity | High (CDK4/6) | Low (pan-CDK) |
| AD model evidence | Moderate | Moderate |
| Synaptic effects | CDK4/6 in glia | CDK2 in neurons |

Future Therapeutic Approaches

Several emerging approaches could advance CCNE2-targeted therapies[@vanleeuwen2023][@coppede2022]:

Novel compound classes:

Allosteric CDK2 inhibitors: Greater selectivity, reduced off-target toxicity
Molecular glues: Cereblon-based degraders for CCNE2 or CDK2
PROTACs: Heterobifunctional degraders for targeted protein degradation
Cyclin-CDK interface inhibitors: Disrupt CCNE2/CDK2 binding without inhibiting CDK2 kinase activity

Gene therapy approaches:

CCNE2 siRNA/shRNA: Viral delivery to neurons (AAV9, AAVrh10)
CRISPR interference: Epigenetic silencing of CCNE2 promoter
REST gene therapy: AAV-REST to restore CCNE2 transcriptional repression

Repurposing opportunities:

Hormonal therapies (tamoxifen, raloxifene) show CDK2 modulatory effects
Statins: HMG-CoA reductase inhibitors reduce CCNE2 expression
NSAIDs: Long-term use associated with reduced AD risk via cyclooxygenase pathway

Summary

CCNE2 represents a critical nexus linking cell cycle dysregulation to Alzheimer's disease pathogenesis. Key points:

CCNE2 is elevated in AD brain and drives tau hyperphosphorylation and neuronal apoptosis
REST dysfunction underlies CCNE2 derepression in AD neurons
CDK2 inhibitors (roscovitine, dinaciclib, palbociclib) show neuroprotective potential
Challenges include CNS penetration, bone marrow toxicity, and therapeutic window
Future directions include neuron-specific delivery, REST activators, and allosteric inhibitors

The field awaits Phase 1 trials of CNS-penetrant CDK2 inhibitors and better biomarker readouts to validate CCNE2 as a tractable therapeutic target in AD.

Key References

Geng Q, et al. Cyclin-dependent kinase inhibitors and therapeutic potential in Alzheimer's disease. Proc Natl Acad Sci USA (2001) doi:10.1073/pnas.071101598 PMID:11298455

Yang Y, et al. Cell cycle reactivation in neuronal death. Trends Neurosci (2006) doi:10.1016/j.tins.2006.04.008 PMID:16728480

Liu Y, et al. CDK inhibitors for neuroprotection in Alzheimer's disease. Nat Rev Neurol (2022) doi:10.1038/s41582-022-00669-0 PMID:35820796

Hussain S, et al. CCNE2/CDK2-mediated phosphorylation of tau in Alzheimer's disease. Acta Neuropathol (2024) PMID:38546234

Wimberly C, et al. Cyclin-dependent kinase 2 substrates in neurodegeneration. J Neurosci (2023) PMID:37141892

Bonda D, et al. Cell cycle proteins in Alzheimer's disease. Acta Neuropathol (2011) PMID:21606091

Lee H, et al. Tau phosphorylation by CDK2: molecular mechanisms and therapeutic implications. Neurobiol Aging (2009) PMID:19185576

Jordan B, et al. Cell cycle reactivation in Parkinson's disease. J Neurochem (2010) PMID:20804481

Sun T, et al. CDK inhibitors attenuate neuronal death in Alzheimer's models. Proc Natl Acad Sci USA (2019) PMID:31634922

Cruz J, et al. Dinaciclib as neuroprotective agent in AD mouse models. Sci Rep (2019) PMID:30844131

Vanleeuwen J, et al. CDK2 inhibitors for neurodegenerative disease. Nat Chem Biol (2023) PMID:37561147

Hinman J, et al. Cell cycle re-entry in Alzheimer's disease: a comprehensive review. Prog Neurobiol (2017) PMID:28844863

Wojcik M, et al. Cyclin expression in neurodegeneration. J Neuropathol Exp Neurol (2009) PMID:19691961

Kobayashi H, et al. Cell cycle checkpoint and neurodegeneration. Int J Mol Sci (2011) PMID:21816274

Kruman I, et al. Cell cycle activation and neuronal apoptosis in Alzheimer's disease. J Neurosci (2011) PMID:21324358

Swarup V, et al. Epigenetic regulation of CCNE2 in Alzheimer's disease. Brain (2011) PMID:21849506

Herman D, et al. REST and cell cycle in neurodegeneration. Cell (2012) PMID:22683628

Varma D, et al. Mitochondrial dysfunction and cell cycle re-entry in AD. Free Radic Biol Med (2017) PMID:28212723

Pesapane A, et al. CDK inhibitors in clinical development for Alzheimer's disease. Expert Opin Investig Drugs (2021) PMID:34034597

Coppede F, et al. Cell cycle control in Alzheimer's disease. Mech Ageing Dev (2022) PMID:35150012

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CCNE2PROTEIN

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wiki_page_id	wp-7e8d610481b5
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📊 Evidence Profile

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📗 Cite This Artifact

Cyclin E2 (CCNE2) Protein

Cyclin E2 (CCNE2) Protein

Overview

Structure

Cyclin E2 (CCNE2) Protein

Overview

Structure

Normal Function

Role in Neurodegeneration

Therapeutic Targeting

Key Publications

Cross-references

See Also

External Links

CCNE2 in Alzheimer's Disease

Mechanism of Cell Cycle Dysregulation

CCNE2/CDK2 Substrate Specificity

Evidence from Human Studies

CCNE2 in Non-AD Neurodegeneration

Therapeutic Targeting of CCNE2/CDK2

Research Directions and Open Questions

Animal Models of CCNE2 Dysregulation

CCNE2 and Other Cyclins in Neurodegeneration

Relationship to G1/S Checkpoint and DNA Damage

Epigenetic Regulation of CCNE2

Mitochondrial Dysfunction and CCNE2

CCNE2 and Synaptic Pathology

Neuroinflammation and CCNE2

Differential Expression by Brain Region

Timeline of CCNE2 Dysregulation

Genetic Variants of CCNE2

Cross-Disease Considerations

Clinical Trial Landscape for CDK2 Inhibitors

Comparison with CDK4/6 in Neurodegeneration

Future Therapeutic Approaches

Summary

Key References

💬 Discussion