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NOVEL RECEPTORS FOR ALPHA SYNUCLEIN AGGREGATES: IMPLICATIONS IN PARKINSON DISEASE PATHOLOGY
Azucena Pérezand 7 co-authors
University of Valencia
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS03-08AM-074
Presentation
Date TBA
Board: PS03-08AM-074
Event Information
Poster Board
PS03-08AM-074
Poster
View posterAbstract
α-Synuclein (α-syn) fibrils accumulate in Parkinson's disease, spreading between cells to template misfolding and drive neurodegeneration. α-Syn fibril entry into healthy neurons is a key step. Here, we comprehensively assessed the membrane proteome for α-syn fibril binding. We identified mGluR4 and NPDC1 as nigral surface proteins binding and internalizing α-syn fibrils. While striatal α-syn fibril injection led to nigral dopamine neuron loss in wild type mice, deletion of either Grm4 or Npdc1 provided protection of dopamine neurons. We observed mGluR4 and Npdc1 to form a complex regulating mGluR4 function. Cultured neurons lacking both Grm4 and Npdc1 fail to bind α-syn fibrils, to accumulate phosphorylated α-syn and to lose synapses. Transheterozygous Grm4, Npdc1 mice showed protection of nigral neurons from α-syn fibrils, demonstrating genetic interaction. For transgenic α-syn A53T mice, double Grm4, Npdc1 heterozygosity increased mouse survival, motor function and spinal motoneuron number. Thus, a cell surface mGluR4-NPDC1 complex participates in α-syn neurodegeneration.
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