mechanism 2,946 words KG: ent-gene-a90f5952 2026-03-24
kind:mechanismsection:mechanismsstate:publishedevidence:strong
Contents

VPS35/Retromer Pathway in Parkinson's Disease

🔬 Protein Info
Gene Symbolent-gene-a90f5952
VPS35 (Vacuolar Protein Sorting 35)The 796-amino acid scaffold protein that forms the central core of the complex
VPS26 (VPS26A/VPS26B)A subunit that recognizes cargo proteins through specific recognition motifs
VPS29A subunit that coordinates the assembly and function of the complex
Amyloid precursor protein (APP)Central to Alzheimer's disease pathogenesis
Dopamine transporter (DAT)Essential for dopamine reuptake
TREM2Microglial receptor involved in amyloid clearance
LRRK2Leucine-rich repeat kinase 2, another PD-associated protein
InheritanceAutosomal dominant
PenetranceHigh (near complete by age 80)
Age of onsetTypically 50-65 years
Clinical phenotypeIndistinguishable from idiopathic PD
Response to levodopaGenerally good
Endosomal cargo accumulationAccumulation of undigested materials within swollen endosomes
Lysosomal enzyme misroutingImpaired delivery of hydrolytic enzymes to lysosomes
Autophagic dysfunctionDisrupted protein clearance through the autophagy-lysosome pathway
KG Connections2 knowledge graph edges
DatabasesGeneCardsUniProtNCBI GeneHPASTRING

Knowledge Graph

Related Hypotheses (23)

Bacterial Enzyme-Mediated Dopamine Precursor Synthesis
Score: 0.36
TREM2-mediated microglial tau clearance enhancement
Score: 0.49
TREM2 Conformational Stabilizers for Synaptic Discrimination
Score: 0.41
Transcriptional Autophagy-Lysosome Coupling
Score: 0.66
Enhancing Vagal Cholinergic Signaling to Restore Gut-Brain A
Score: 0.51

Related Analyses (30)

Astrocyte reactivity subtypes in neurodegeneration
neurodegeneration · archived
Blood-brain barrier transport mechanisms for antibody therap
neurodegeneration · archived
Neuroinflammation resolution mechanisms and pro-resolving me
neurodegeneration · archived
What are the mechanisms by which gut microbiome dysbiosis in
neurodegeneration · archived
RNA binding protein dysregulation across ALS FTD and AD
neurodegeneration · archived

Related Experiments (30)

ER-Golgi Secretory Pathway Dysfunction in PD - Experiment De
clinical · proposed · Score: 0.40
AAV Serotype Comparison for LRRK2 Knockdown in PD Gene Thera
validation · proposed · Score: 0.40
AAV-LRRK2 IND-Enabling Study Design
clinical · proposed · Score: 0.40
AAV Serotype Comparison for LRRK2 Knockdown in PD
validation · proposed · Score: 0.40
Alpha-Synuclein SAA Kinetics Study — Biological Staging Back
clinical · proposed · Score: 0.40

Knowledge Graph (2 edges)

ent-gene-a90f5952 data_in benchmark_ot_ad_answer_key:VPS35
benchmark_ot_ad_answer_key:VPS35 data_in ent-gene-a90f5952