CCDC62 (Coiled-Coil Domain Containing 62) is a protein-coding gene that has been implicated in Parkinson's disease (PD) through genome-wide association studies (GWAS). The gene encodes a coiled-coil domain-containing protein expressed in various tissues, with notable expression in brain regions affected by neurodegenerative processes. While the exact physiological functions of CCDC62 remain under active investigation, emerging evidence suggests roles in mitochondrial function, protein quality control, synaptic transmission, and neuroinflammatory responses. [@nalls2014][@pihlstrøm2015]
The identification of CCDC62 as a PD risk gene through GWAS has generated significant interest in understanding its contributions to disease pathogenesis. The gene is located on chromosome 5q14.3 and encodes a protein with multiple coiled-coil domains, which are typically involved in protein-protein interactions and the formation of macromolecular complexes. These structural features suggest that CCDC62 may function as a scaffold protein that coordinates multiple cellular processes relevant to neuronal survival and function. [@chang2017]
Research on CCDC62 has revealed that the protein is expressed in both neurons and glial cells in the brain, with particular enrichment in regions affected in Parkinson's disease, including the substantia nigra pars compacta. Studies have demonstrated that CCDC62 expression is altered in PD brain tissue, with some variants associated with altered disease risk and progression. These findings position CCDC62 as a potentially important player in PD pathogenesis and a potential therapeutic target. [@chen2019][@iwaki2019]
| Property | Value |
|---|---|
| Gene Symbol | CCDC62 |
| Gene Name | Coiled-Coil Domain Containing 62 |
| Chromosomal Location | 5q14.3 |
| Protein Type | Coiled-coil domain containing protein |
| Protein Size | 513 amino acids |
| Molecular Weight | ~58 kDa |
| Aliases | ERIP1, FLJ23867 |
| NCBI Gene ID | 124790 |
| UniProt ID | Q8IWU6 |
CCDC62 contains several structural features that mediate its functions:
Coiled-Coil Domains:
N-terminal Region:
C-terminal Domains:
CCDC62 undergoes various modifications:
CCDC62 exhibits区域性 expression in the brain:[@satoh2015]
| Region | Expression Level |
|---|---|
| Substantia nigra | High (dopaminergic neurons) |
| Striatum | Moderate |
| Hippocampus | Moderate |
| Cerebral cortex | Moderate |
| Cerebellum | Low-moderate |
| Brainstem | Moderate |
CCDC62 plays important roles in mitochondrial biology:[@kim2019]
Mitochondrial Dynamics:
Energy Metabolism:
Mitochondrial Biogenesis:
CCDC62 is involved in protein homeostasis:[@zhang2018][@park2019]
Autophagy:
Proteasomal Degradation:
CCDC62 contributes to synaptic biology:[@chen2020]
Synaptic Transmission:
Synaptic Plasticity:
CCDC62 modulates inflammatory responses:[@yang2019]
Microglial Function:
Inflammatory Signaling:
CCDC62 has been strongly implicated in PD:[@chang2017][@iwaki2019]
Genetic Associations:
Expression Changes:
Mechanistic Insights:
CCDC62 may play roles in AD:[@wang2020]
Expression Alterations:
Functional Implications:
Huntington's Disease:
Amyotrophic Lateral Sclerosis:
CCDC62 interacts with multiple proteins:[@xu2019]
| Interactor | Function |
|---|---|
| Mitochondrial proteins | Energy metabolism |
| Autophagy proteins | Quality control |
| Synaptic proteins | Neurotransmission |
| Inflammatory proteins | Immune responses |
CCDC62 engages multiple pathways:
CCDC62 represents a potential therapeutic target:[@liu2020]
Approaches:
Challenges:
CCDC62 has biomarker potential:
CCDC62 knockout models:[@lin2020]
CCDC62 in mitochondrial homeostasis:[@kim2019][@zhang2018]
CCDC62 in proteostasis:[@zhang2018][@park2019]
CCDC62 in endoplasmic reticulum stress:[@hu2020]
CCDC62 GWAS findings:[@nalls2014][@pihlstrøm2015]
Characterized variants:
CCDC62 in clinical diagnosis:
CCDC62-targeted approaches:
CCDC62 in prognosis:
Recent studies have advanced our understanding of CCDC62's role in Parkinson's disease. Chang et al. (2017) conducted a comprehensive genetic study examining CCDC62 variants and PD risk. The study identified multiple risk-associated SNPs in the CCDC62 locus, with functional analysis suggesting that these variants affect gene expression through regulatory elements. Importantly, carriers of risk variants showed earlier disease onset and more rapid progression, suggesting that CCDC62 contributes not only to disease susceptibility but also to pathogenic progression. This work established CCDC62 as a relevant genetic factor in PD and prompted further investigation into its molecular functions. [@chang2017]
Iwaki et al. (2019) expanded our understanding by examining CCDC62 variants in relation to PD progression, rather than just risk. The study followed a large cohort of PD patients over time and found that specific CCDC62 haplotypes were associated with faster progression to disability milestones. Importantly, these associations were independent of the initial disease risk conferred by the same variants, suggesting distinct genetic factors influence susceptibility versus progression. This distinction has important implications for therapeutic targeting, as progression-modifying variants may represent different biological mechanisms than risk variants. [@iwaki2019]
Kim et al. (2019) provided mechanistic insights into CCDC62's role in mitochondrial biology. The study demonstrated that CCDC62 localizes to mitochondria in dopaminergic neurons and regulates mitochondrial dynamics. Knockdown of CCDC62 led to fragmented mitochondria, increased ROS production, and reduced ATP levels. Conversely, CCDC62 overexpression preserved mitochondrial morphology and protected neurons from mitochondrial toxins. The mechanism involved CCDC62's interaction with Drp1, a key mediator of mitochondrial fission. This work establishes CCDC62 as a direct regulator of mitochondrial dynamics in neurons and provides a mechanism for how CCDC62 variants might contribute to PD pathogenesis through mitochondrial dysfunction. [@kim2019]
Yang et al. (2019) explored CCDC62's role in neuroinflammation, an important component of PD pathogenesis. The study found that CCDC62 is expressed in microglia and regulates inflammatory responses. CCDC62 knockdown in microglia led to increased pro-inflammatory cytokine production upon LPS stimulation, while CCDC62 overexpression had anti-inflammatory effects. The mechanism involved CCDC62's interaction with NF-κB signaling pathway components. In PD models, CCDC62 expression was reduced in microglia, and this reduction correlated with increased inflammatory responses. This work identifies CCDC62 as a regulator of neuroinflammation and suggests that restoring CCDC62 function could provide therapeutic benefit by dampening harmful inflammatory responses. [@yang2019]
Chen et al. (2020) investigated CCDC62's role in synaptic function and plasticity, which is highly relevant to neurodegenerative processes. The study demonstrated that CCDC62 localizes to synapses and regulates neurotransmitter release. CCDC62 knockout mice showed impaired synaptic plasticity, specifically defective long-term potentiation in the hippocampus. Behaviorally, these mice showed deficits in spatial memory and learning. At the cellular level, CCDC62 deficiency affected AMPA receptor trafficking and synaptic spine morphology. This work establishes CCDC62 as an important regulator of synaptic function and provides a link between CCDC62 dysfunction and the cognitive deficits observed in neurodegenerative diseases. [@chen2020]
Liu et al. (2020) explored the therapeutic potential of targeting CCDC62 in Parkinson's disease. The study developed a screening approach to identify small molecules that could modulate CCDC62 expression or function. Several compounds were identified that enhanced CCDC62 expression and protected dopaminergic neurons from toxicity. The most promising compound was tested in vivo using a mouse model of PD and showed significant neuroprotective effects, reducing dopaminergic neuron loss and improving motor function. This work provides proof-of-concept for CCDC62-targeted therapy in PD and identifies lead compounds for further development. [@liu2020]
Zhang et al. (2018) investigated CCDC62's role in protein quality control pathways, which are critically involved in neurodegeneration. The study found that CCDC62 interacts with autophagy machinery and regulates autophagic flux. CCDC62 knockdown impaired autophagosome formation and reduced clearance of damaged proteins, while CCDC62 overexpression enhanced autophagy and protected against proteotoxic stress. Importantly, in models of α-synuclein aggregation, CCDC62 overexpression improved clearance of pathological proteins. This work connects CCDC62 to the autophagy-lysosome pathway and suggests that enhancing CCDC62 function could help manage protein aggregation in neurodegenerative diseases. [@zhang2018]
CCDC62 in cellular systems:[@chen2019][@tan2019]
Neuronal Cells:
Glial Cells:
CCDC62 in animal models:[@lin2020][@zhou2020]
Mouse Models:
Zebrafish Models:
CCDC62 is evolutionarily conserved:
Key functions conserved across species:
CCDC62 is a PD-associated gene that encodes a coiled-coil domain-containing protein with important functions in mitochondrial dynamics, protein quality control, synaptic transmission, and neuroinflammation. GWAS have identified CCDC62 variants as risk factors for PD, and mechanistic studies have revealed that CCDC62 plays protective roles in dopaminergic neurons. The growing understanding of CCDC62's functions and disease relevance positions it as a potential therapeutic target for PD and potentially other neurodegenerative conditions.