Elsevier Inc. potential HD lncRNA ---> Huntington Disease QUIN ---> Huntington Disease potential HD lncRNA upregulated miRNA upregulated miRNA ---> downregulated target translation downregulated target translation downregulated miRNA ---> upregulated target translation downregulated miRNA upregulated target translation potential HD miRNA ex-Grin2b loss of projecting cortical neurons potential HD miRNA ---> Huntington Disease loss of striatal SPNs Huntington Disease QUIN Grin2b D2 SPNs D1 SPNs brain-derived neurotrophic factor signaling pathway Dnm1l KYNA 3-HANA 3-HK kynurenine metabolic pathway microglia astrocyte neuroinflammatory responses --+> microglia HTT interacting proteins shorter, toxic fragments cell homeostasis transcription vesicular trafficking Rest ---| BDNF transcription Rest Htt ---> cell homeostasis Rasd2 interacting proteins Htt DNA modification pathway dorsal striatal SPNs neurons mHtt Casp6 1-586 fragment NMDAR-mediated excitotoxicity Ntrk2 mHtt ---- Rasd2 neuroinflammatory responses polyQ RNA polymerase II transcription pathway histone modification pathway electron transport chain pathway autophagy pathway Htt ---> transcription Htt ---> mitochondria function Htt ---> vesicular trafficking mHtt ---| BDNF transcription Bdnf BDNF transcription Bdnf ---- Ntrk2 BDNF transport aa1-17 mitochondria function Casp6 ---> PRD mitochondria dynamics pathway mHtt ---| Rasd2 Rasd2 ---- Rasd2 interacting proteins brain-derived neurotrophic factor signaling pathway ---> D1 SPNs Rasd2 brain-derived neurotrophic factor signaling pathway --+> D2 SPNs mHtt ---| electron transport chain pathway mHtt ---| autophagy pathway Crebbp brain-derived neurotrophic factor signaling pathway ---> dorsal striatal SPNs neurons mHtt ---| mitochondria dynamics pathway Htt ---- HTT interacting proteins HTT interacting proteins ---- mHtt Rasd2 ---> mHtt Htt ---| Rest mHtt ---| brain-derived neurotrophic factor signaling pathway mHtt ---| BDNF transport Htt --+> BDNF transport Crebbp ---> histone modification pathway Crebbp ---> RNA polymerase II transcription pathway Crebbp ---> DNA modification pathway mHtt ---| Crebbp Crebbp ---- mHtt Dnm1l ---- mHtt aa69-3144, HEAT repeat domains, PEST domains in disordered regions polyQ ---> Htt polyQ ---> mHtt mHtt ---> ex-Grin2b mHtt ---> Huntington Disease PRD