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.
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.
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<sup>[1]</sup>. PSD-95 is essential for synaptic structure, function, and plasticity, serving as a critical organizer of the postsynaptic density (PSD)<sup>[2]</sup>. 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).
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
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
Hunt CA, et al. (2013). "Altered PSD-95 expression and function in animal models of Alzheimer's disease." Neurobiol Aging. 34(10):2343-2354. PMID: 23597878(https://pubmed.ncbi.nlm.nih.gov/23597878/)
Coley AA, et al. (2020). "PSD-95 deficiency alters GABAergic signaling in an Alzheimer's disease model." J Neurosci. 40(45):8701-8715. PMID: 32973063(https://pubmed.ncbi.nlm.nih.gov/32973063/)
Kim E, et al. (1997). "PSD-95: Interaction with the synaptic receptor complex." Nature. 387(6633):634-638. PMID: 9177353(https://pubmed.ncbi.nlm.nih.gov/9177353/)
Migaud M, et al. (1998). "Enhanced [long-term potentiation](/mechanisms/long-term-potentiation) and impaired learning in mice with mutant PSD-95." Nature. 396(6709):433-439. PMID: 9853559(https://pubmed.ncbi.nlm.nih.gov/9853559/)
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