DLG4 Gene - PSD-95

DLG4 Gene

Introduction

Dlg4 Gene Psd 95 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@kim1997]
<table> [@migaud1998]
<tr><th colspan="2" style="background:#f0f0f0;">DLG4</th></tr> [@coley2020]
<tr><td><b>Full Name</b></td><td>Discs Large Homolog 4 / PSD-95</td></tr> [@psd2011]
<tr><td><b>Chromosomal Location</b></td><td>8p21.2</td></tr>
<tr><td><b>NCBI Gene ID</b></td><td>[1749](https://www.ncbi.nlm.nih.gov/gene/1749)</td></tr>
<tr><td><b>OMIM</b></td><td>[603424](https://www.omim.org/entry/603424)</td></tr>
<tr><td><b>Ensembl ID</b></td><td>ENSG00000132587</td></tr>
<tr><td><b>UniProt ID</b></td><td>[P78352](https://www.uniprot.org/uniprot/P78352)</td></tr>
<tr><td><b>Associated Diseases</b></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Autism Spectrum Disorder](/diseases/autism-spectrum-disorder), [Schizophrenia](/diseases/schizophrenia), [Amyotrophic Lateral Sclerosis](/diseases/als)</td></tr>
</table>
</div>

Overview

DLG4 Gene

Introduction

Dlg4 Gene Psd 95 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@kim1997]
<table> [@migaud1998]
<tr><th colspan="2" style="background:#f0f0f0;">DLG4</th></tr> [@coley2020]
<tr><td><b>Full Name</b></td><td>Discs Large Homolog 4 / PSD-95</td></tr> [@psd2011]
<tr><td><b>Chromosomal Location</b></td><td>8p21.2</td></tr>
<tr><td><b>NCBI Gene ID</b></td><td>[1749](https://www.ncbi.nlm.nih.gov/gene/1749)</td></tr>
<tr><td><b>OMIM</b></td><td>[603424](https://www.omim.org/entry/603424)</td></tr>
<tr><td><b>Ensembl ID</b></td><td>ENSG00000132587</td></tr>
<tr><td><b>UniProt ID</b></td><td>[P78352](https://www.uniprot.org/uniprot/P78352)</td></tr>
<tr><td><b>Associated Diseases</b></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Autism Spectrum Disorder](/diseases/autism-spectrum-disorder), [Schizophrenia](/diseases/schizophrenia), [Amyotrophic Lateral Sclerosis](/diseases/als)</td></tr>
</table>
</div>

Overview

DLG4 (Discs Large Homolog 4) encodes PSD-95 (Postsynaptic Density Protein 95), one of the most abundant scaffold proteins at excitatory synapses in the brain^[1]. PSD-95 is essential for synaptic structure, function, and plasticity, serving as a critical organizer of the postsynaptic density (PSD)^[2]. Dysregulation of DLG4/PSD-95 is implicated in various neurodegenerative and neuropsychiatric disorders including [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [Autism Spectrum Disorder](/diseases/autism-spectrum-disorder), and [Schizophrenia](/diseases/schizophrenia).

Function

DLG4/PSD-95 performs critical synaptic functions^[3]:

• Synaptic scaffolding: Organizes the postsynaptic density by anchoring [NMDA](/entities/nmda-receptor) receptors, AMPA receptors, and other signaling proteins
• Synaptic transmission: Regulates glutamate receptor trafficking and function at excitatory synapses
• Synaptic plasticity: Essential for [long-term potentiation](/mechanisms/long-term-potentiation) (LTP) and long-term depression (LTD) induction
• Dendritic spine formation: Controls spine morphology, density, and stability
• Signal transduction: Links receptors to downstream signaling molecules (CaMKII, nNOS)
• Anchoring proteins: Binds to various synaptic proteins via PDZ domains

Protein Structure

PSD-95 contains multiple functional domains:

• PDZ domains (PDZ1-3): Three PDZ domains that bind to C-terminal motifs of target proteins
• SH3 domain: Src homology 3 domain for protein-protein interactions
• GK domain: Guanylate kinase-like domain that binds to other PSD-95 molecules
• N-terminal palmitoylation site: Targets PSD-95 to synaptic membranes

Disease Associations

[Alzheimer's Disease](/diseases/alzheimers-disease)

DLG4/PSD-95 is significantly affected in AD^[4]:

• Reduced expression: PSD-95 levels are decreased in AD brain, correlating with synaptic loss
• Altered localization: Abnormal distribution of PSD-95 in [dendritic spines](/cell-types/dendritic-spines)
• [Tau](/proteins/tau) pathology: Phosphorylated [tau](/proteins/tau) interacts with PSD-95, disrupting synaptic organization
• [Aβ](/proteins/amyloid-beta) effects: Amyloid-beta reduces PSD-95 expression and disrupts synaptic plasticity
• NMDA receptor dysregulation: Altered PSD-95-NMDAR coupling contributes to excitotoxicity
• Cognitive correlation: PSD-95 loss correlates with cognitive decline in AD patients

[Parkinson's Disease](/diseases/parkinsons-disease)

• Synaptic alterations: PSD-95 changes in dopaminergic brain regions
• [Alpha-synuclein](/proteins/alpha-synuclein) interaction: α-Synuclein may affect PSD-95 function
• Excitotoxicity: Dysregulated glutamate signaling contributes to dopaminergic neuron loss

[Autism Spectrum Disorder](/diseases/autism-spectrum-disorder)

• Genetic variants: DLG4 variants associated with ASD risk
• Synaptic dysfunction: Altered PSD-95 function affects synaptic development
• Social behavior: PSD-95 knockout mice show social behavior deficits

[Schizophrenia](/diseases/schizophrenia)

• Expression changes: Altered PSD-95 expression in schizophrenia brain
• NMDA receptor signaling: Dysregulated PSD-95-NMDAR signaling implicated
• Cognitive deficits: PSD-95 alterations contribute to cognitive symptoms

[Amyotrophic Lateral Sclerosis](/diseases/als)

• Motor neuron synapses: PSD-95 changes at motor neuron synapses
• Excitotoxicity: Altered glutamate receptor anchoring contributes to excitotoxic cell death

Therapeutic Targeting

PSD-95 is a therapeutic target for neurodegenerative diseases:

Current Approaches

• PSD-95 inhibitors: Small molecules that disrupt PSD-95-protein interactions
• NMDA receptor modulators: Targeting PSD-95-NMDAR coupling
• Synaptic stabilizers: Compounds that preserve synaptic structure

Research Directions

• Gene therapy: Delivering DLG4 or PSD-95 stabilizing molecules
• Protein-protein interaction blockers: Developing specific inhibitors
• Phosphorylation modulators: Targeting PSD-95 phosphorylation states

Key Publications

Background

The study of Dlg4 Gene Psd 95 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Brain Atlas Resources

• [Allen Human Brain Atlas - DLG4 Expression](https://human.brain-map.org/microarray/search/show?search_term=DLG4): Gene expression data across brain regions
• [Allen Cell Type Atlas](https://celltypes.brain-map.org/): Cellular expression patterns in [neurons](/entities/neurons) and glia
• [BrainSpan - DLG4 Developmental Expression](https://brainspan.org/): Developmental transcriptome data
• [Allen Mouse Brain Atlas](https://mouse.brain-map.org/): Mouse brain expression data

See Also

• PSD-95 Protein
• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease-disease)
• [Autism Spectrum Disorder](/diseases/autism-spectrum-disorder)
• [Schizophrenia](/diseases/schizophrenia)
• [Amyotrophic Lateral Sclerosis](/diseases/amyotrophic-lateral-sclerosis)
• [Synaptic Dysfunction Pathway](/mechanisms/synaptic-dysfunction)
• [NMDA Receptors](/mechanisms/glutamatergic-signaling)
• [Synaptic Plasticity](/mechanisms/synaptic-plasticity)

Pathway Diagram

The following diagram shows the key molecular relationships involving DLG4 Gene - PSD-95 discovered through SciDEX knowledge graph analysis: