HSPG2 and Parkinson disease: In the central nervous system, irisin and FNDC5 form a functional axis upstream of BDNF, in which PGC-1–driven FNDC5 expression and subsequent irisin signaling increase BDNF transcription and TrkB-dependent activation of MAPK, PI3K, and PLC-pathways, thereby supporting neuronal survival, synaptic plasticity, and cognitive performance in both experimental PD and other neurodegenerative settings [23].