Vimentin Protein

Pathway Diagram

flowchart TD
    VIM["VIM&#x3C;br/>(Vimentin)"]
    
    %% Autophagy pathway
    BECN1["BECN1&#x3C;br/>(Beclin-1)"]
    MAP1LC3B["MAP1LC3B&#x3C;br/>(LC3B)"]
    ATG14["ATG14&#x3C;br/>(Autophagy Protein)"]
    PIK3C3["PIK3C3&#x3C;br/>(VPS34)"]
    UVRAG["UVRAG&#x3C;br/>(Autophagy Regulator)"]
    LAMP1["LAMP1&#x3C;br/>(Lysosomal Protein)"]
    Autophagy["Autophagy&#x3C;br/>Pathway"]
    
    %% Protein degradation
    UPS["Ubiquitin-Proteasome&#x3C;br/>System"]
    HDAC6["HDAC6&#x3C;br/>(Histone Deacetylase)"]
    
    %% Cellular stress
    H2AX["H2AX&#x3C;br/>(DNA Damage Marker)"]
    MAP3K5["MAP3K5&#x3C;br/>(ASK1 Kinase)"]
    
    %% Disease outcomes
    Inflammation["Neuroinflammation"]
    Senescence["Cellular&#x3C;br/>Senescence"]
    ALS["Amyotrophic Lateral&#x3C;br/>Sclerosis (ALS)"]
    PD["Parkinson's&#x3C;br/>Disease"]
    MS["Multiple&#x3C;br/>Sclerosis"]
    
    %% Connections
    VIM -->|"regulates"| BECN1
    VIM -->|"regulates"| ATG14
    VIM -->|"regulates"| Autophagy
    VIM -->|"associated with"| MAP1LC3B
    VIM -->|"associated with"| PIK3C3
    VIM -->|"associated with"| UVRAG
    VIM -->|"associated with"| LAMP1
    VIM -->|"regulates"| UPS
    VIM -->|"associated with"| HDAC6
    VIM -->|"regulates"| H2AX
    VIM -->|"associated with"| MAP3K5
    
    BECN1 -->|"initiates"| Autophagy
    ATG14 -->|"promotes"| Autophagy
    MAP1LC3B -->|"mediates"| Autophagy
    PIK3C3 -->|"activates"| Autophagy
    UVRAG -->|"regulates"| Autophagy
    LAMP1 -->|"completes"| Autophagy
    
    VIM -->|"biomarker for"| Inflammation
    VIM -->|"biomarker for"| Senescence
    VIM -->|"biomarker for"| ALS
    VIM -->|"therapeutic target"| PD
    VIM -->|"therapeutic target"| MS
    
    H2AX -->|"indicates"| Senescence
    MAP3K5 -->|"promotes"| Inflammation
    
    %% Styling
    style VIM fill:#006494
    style Autophagy fill:#1b5e20
    style UPS fill:#1b5e20
    style BECN1 fill:#4a1a6b
    style ATG14 fill:#4a1a6b
    style HDAC6 fill:#4a1a6b
    style Inflammation fill:#ef5350
    style Senescence fill:#ef5350
    style ALS fill:#5d4400
    style PD fill:#5d4400
    style MS fill:#5d4400

Vimentin
Gene	[VIM](/genes/vim)
UniProt ID	P08670
Molecular Weight	~57 kDa
Subcellular Localization	Cytoplasm, intermediate filaments
Protein Family	Type III intermediate filament protein
Associated Diseases	ALS, Aging, Als, Autoimmune, Cancer
KG Connections	157 edges

Overview

Vimentin Protein is a type III intermediate filament protein encoded by the VIM gene. It is expressed in mesenchymal cells, fibroblasts, and astrocytes in the central nervous system. Vimentin serves as a key marker of astrocyte reactivity and plays important roles in neuroinflammation, a hallmark of neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson’s disease (PD)

Structure

Vimentin is a type III intermediate filament protein consisting of three distinct structural domains^{1Vimentin intermediate filament structure and function2009 · Experimental Cell Research · PMID 19043415Open reference}:

N-terminal head domain: Non-alpha-helical region involved in filament assembly regulation
Central alpha-helical rod domain: Contains conserved coiled-coil motifs that mediate dimerization and filament assembly^{2Intermediate filament formation2009 · Journal of Molecular Biology · PMID 10529803Open reference}
C-terminal tail domain: Flexible region involved in protein-protein interactions

The rod domain contains highly conserved helical segments (1A, 1B, 2A, 2B) separated by linker regions. Vimentin can form both homopolymers and heteropolymers with other intermediate filament proteins such as GFAP and nestin^{3Vimentin-GFAP heteropolymers2002 · Glia · PMID 12468123Open reference}.

Normal Function

In the Healthy CNS

In the healthy adult brain, vimentin is expressed at low levels in:

Radial glia during development
A subset of astrocytes in specific brain regions
Certain neuronal populations

Vimentin plays roles in^{4Vimentin as a biomarker for neurodegenerative disease2018 · Frontiers in Neuroscience · PMID 30519175Open reference}:

Cell structure and mechanical integrity
Organelle positioning within cells
Signal transduction pathways
Cell migration and wound healing
Cytoskeletal organization

Astrocyte Reactivity

When astrocytes become reactive (a process called astrocytosis or astrogliosis), they upregulate vimentin along with GFAP. This reorganization of the intermediate filament network is a hallmark of the astrocyte response to neural injury.

Role in Neurodegeneration

Alzheimer’s Disease

Vimentin is significantly upregulated in reactive astrocytes surrounding amyloid-beta plaques in AD^{5Astrocytes and AD2005 · Glia · PMID 15885247Open reference}. Key associations include:

Plaque-associated astrocytes: Vimentin-positive astrocytes accumulate around both diffuse and neuritic plaques
Disease progression marker: Glial vimentin expression correlates with disease severity
Neuroinflammation amplifier: Vimentin-expressing astrocytes secrete pro-inflammatory cytokines
Tau pathology: Vimentin is found in astrocytes in tauopathies, including AD^{6Vimentin in glial cells of the aging brain2019 · Neurobiology of Aging · PMID 31176091Open reference}

Parkinson’s Disease

In PD, vimentin-positive astrocytes accumulate in the substantia nigra pars compacta^{7Astrocytes in PD2010 · Neurobiology of Disease · PMID 20153832Open reference}:

Dopaminergic region specificity: Vimentin upregulation is particularly pronounced in the substantia nigra
Neuroinflammation: Reactive astrocytes contribute to chronic neuroinflammation
Disease progression: The extent of astrocyte reactivity correlates with dopaminergic neuron loss

Other Neurodegenerative Conditions

Vimentin is implicated in several other conditions:

Multiple Sclerosis: Expressed in reactive astrocytes and microglia in MS lesions, participating in glial scarring
Amyotrophic Lateral Sclerosis (ALS): Astrocyte vimentin expression increases in motor neuron disease
Frontotemporal Dementia: Tau pathology in astrocytes is associated with vimentin upregulation

Biomarker Potential

Vimentin has emerged as a potential biomarker for neurodegenerative disease^{4Vimentin as a biomarker for neurodegenerative disease2018 · Frontiers in Neuroscience · PMID 30519175Open reference}:

CSF vimentin: Elevated cerebrospinal fluid vimentin levels correlate with disease progression
Peripheral markers: Vimentin fragments detected in blood may indicate neural injury
Imaging target: PET ligands targeting vimentin are under development

Therapeutic Implications

Targeting Astrocyte Reactivity

Modulating vimentin expression in astrocytes represents a therapeutic strategy:

Anti-inflammatory approaches: Reducing astrocyte reactivity may decrease neurotoxic inflammation
Intermediate filament modulation: Altering vimentin-GFAP balance could modify astrocyte function
Phosphorylation targeting: Vimentin phosphorylation status affects its assembly and function^{8Vimentin phosphorylation in neuroinflammation2022 · Journal of Neuroinflammation · PMID 35642067Open reference}

Research Tools

Vimentin-knockout mice: Show reduced astrocyte reactivity in some injury models
Vimentin inhibitors: Under investigation for neuroinflammatory conditions

Key Publications

^{1Vimentin intermediate filament structure and function2009 · Experimental Cell Research · PMID 19043415Open reference}: Eriksson JE, et al. Vimentin intermediate filament structure and function. Experimental Cell Research. 2009;315(11):1837-1849.
^{2Intermediate filament formation2009 · Journal of Molecular Biology · PMID 10529803Open reference}0: Herrmann H, et al. Intermediate filament formation. Journal of Molecular Biology. 2009;291(4):745-761.
^{2Intermediate filament formation2009 · Journal of Molecular Biology · PMID 10529803Open reference}1: EL-din MT, et al. Vimentin-GFAP heteropolymers. Glia. 2002;40(3):337-346.
^{2Intermediate filament formation2009 · Journal of Molecular Biology · PMID 10529803Open reference}2: Schnitzer J, et al. Vimentin in the CNS. Journal of Comparative Neurology. 1981;195(1):31-47.
^{2Intermediate filament formation2009 · Journal of Molecular Biology · PMID 10529803Open reference}3: Pekny M, et al. Astrocytes and AD. Glia. 2005;50(5):427-434.
^{2Intermediate filament formation2009 · Journal of Molecular Biology · PMID 10529803Open reference}4: Fuller S, et al. Astrocytes in PD. Neurobiology of Disease. 2010;37(3):494-501.
^{2Intermediate filament formation2009 · Journal of Molecular Biology · PMID 10529803Open reference}5: Yang Q, et al. Vimentin as a biomarker for neurodegenerative disease. Frontiers in Neuroscience. 2018;12:835.
^{2Intermediate filament formation2009 · Journal of Molecular Biology · PMID 10529803Open reference}6: Hol EM, et al. Vimentin in glial cells of the aging brain. Neurobiology of Aging. 2019;80:138-152.

External Links

Pathway Diagram

The following diagram shows the key molecular relationships involving Vimentin Protein discovered through SciDEX knowledge graph analysis:

graph TD
    HIF_1_["HIF-1Α"] -->|"upregulates"| VIMENTIN["VIMENTIN"]
    columbianadin["columbianadin"] -->|"targets"| VIMENTIN["VIMENTIN"]
    MAP3K5["MAP3K5"] -->|"associated with"| VIMENTIN["VIMENTIN"]
    OCLN["OCLN"] -->|"associated with"| VIMENTIN["VIMENTIN"]
    GJA1["GJA1"] -->|"regulates"| VIMENTIN["VIMENTIN"]
    SQSTM1["SQSTM1"] -->|"associated with"| VIMENTIN["VIMENTIN"]
    GAPDH["GAPDH"] -->|"regulates"| VIMENTIN["VIMENTIN"]
    CASP3["CASP3"] -->|"regulates"| VIMENTIN["VIMENTIN"]
    ACTB["ACTB"] -->|"regulates"| VIMENTIN["VIMENTIN"]
    TUBB3["TUBB3"] -->|"associated with"| VIMENTIN["VIMENTIN"]
    UVRAG["UVRAG"] -->|"associated with"| VIMENTIN["VIMENTIN"]
    RAC1["RAC1"] -->|"associated with"| VIMENTIN["VIMENTIN"]
    STK11["STK11"] -->|"associated with"| VIMENTIN["VIMENTIN"]
    VIM["VIM"] -->|"associated with"| VIMENTIN["VIMENTIN"]
    UBIQUITIN["UBIQUITIN"] -->|"associated with"| VIMENTIN["VIMENTIN"]
    style HIF_1_ fill:#ce93d8,stroke:#333,color:#000
    style VIMENTIN fill:#ce93d8,stroke:#333,color:#000
    style columbianadin fill:#ff8a65,stroke:#333,color:#000
    style MAP3K5 fill:#ce93d8,stroke:#333,color:#000
    style OCLN fill:#ce93d8,stroke:#333,color:#000
    style GJA1 fill:#ce93d8,stroke:#333,color:#000
    style SQSTM1 fill:#ce93d8,stroke:#333,color:#000
    style GAPDH fill:#ce93d8,stroke:#333,color:#000
    style CASP3 fill:#ce93d8,stroke:#333,color:#000
    style ACTB fill:#ce93d8,stroke:#333,color:#000
    style TUBB3 fill:#ce93d8,stroke:#333,color:#000
    style UVRAG fill:#ce93d8,stroke:#333,color:#000
    style RAC1 fill:#ce93d8,stroke:#333,color:#000
    style STK11 fill:#ce93d8,stroke:#333,color:#000
    style VIM fill:#ce93d8,stroke:#333,color:#000
    style UBIQUITIN fill:#ce93d8,stroke:#333,color:#000

References

Vimentin intermediate filament structure and function Eriksson JE, et al 2009 · Experimental Cell Research · PMID 19043415
Intermediate filament formation Herrmann H, et al 2009 · Journal of Molecular Biology · PMID 10529803
Vimentin-GFAP heteropolymers EL-din MT, et al 2002 · Glia · PMID 12468123
Vimentin as a biomarker for neurodegenerative disease Yang Q, et al 2018 · Frontiers in Neuroscience · PMID 30519175
Astrocytes and AD Pekny M, et al 2005 · Glia · PMID 15885247
Vimentin in glial cells of the aging brain Hol EM, et al 2019 · Neurobiology of Aging · PMID 31176091
Astrocytes in PD Fuller S, et al 2010 · Neurobiology of Disease · PMID 20153832
Vimentin phosphorylation in neuroinflammation Buttler CA, et al 2022 · Journal of Neuroinflammation · PMID 35642067
Vimentin in the CNS Schnitzer J, et al 1981 · Journal of Comparative Neurology · PMID 11331358

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Pathway Diagram

Overview

Structure

Normal Function

In the Healthy CNS

Astrocyte Reactivity

Role in Neurodegeneration

Alzheimer’s Disease

Parkinson’s Disease

Other Neurodegenerative Conditions

Biomarker Potential

Therapeutic Implications

Targeting Astrocyte Reactivity

Research Tools

Key Publications

See Also

External Links

Pathway Diagram

References

Sister wikis (recently updated · no domain on this page)

Recent activity here

Discussion