biostudies-literatureTshilenge KTNIA NIH HHSNINDS NIH HHSNational Institutes of HealthNIH HHS100534https://www.ebi.ac.uk/biostudies/studies/S-EPMC10165459biostudies-literatureUnknown22(5)Huntington's disease (HD) is a neurodegenerative disease caused by a CAG repeat expansion in the Huntingtin (HTT) gene. The resulting polyglutamine (polyQ) tract alters the function of the HTT protein. Although HTT is expressed in different tissues, the medium-spiny projection neurons (MSNs) in the striatum are particularly vulnerable in HD. Thus, we sought to define the proteome of human HD patient-derived MSNs. We differentiated HD72-induced pluripotent stem cells and isogenic controls into MSNs and carried out quantitative proteomic analysis. Using data-dependent acquisitions with FAIMS for label-free quantification on the Orbitrap Lumos mass spectrometer, we identified 6323 proteins with at least two unique peptides. Of these, 901 proteins were altered significantly more in the HD72-MSMolecular & cellular proteomics : MCPProteomic Analysis of Huntington's Disease Medium Spiny Neurons Identifies Alterations in Lipid Droplets.PMC10165459R01-NS100529S10 OD016281R01 NS1005291S10 OD016281S10 OD028654K99 AG065484Loureiro ABattistoni EHetz CRose JTshilenge KTMilani MNaphade SWehrfritz CBasisty NSchilling BBons JLopez-Ramirez AGerencser AASong SAguirre CGMooney SDEllerby LMHoltz AfalseProteomic Analysis of Huntington's Disease Medium Spiny Neurons Identifies Alterations in Lipid Droplets.Huntington's disease (HD) is a neurodegenerative disease caused by a CAG repeat expansion in the Huntingtin (HTT) gene. The resulting polyglutamine (polyQ) tract alters the function of the HTT protein. Although HTT is expressed in different tissues, the medium-spiny projection neurons (MSNs) in the striatum are particularly vulnerable in HD. Thus, we sought to define the proteome of human HD patient-derived MSNs. We differentiated HD72-induced pluripotent stem cells and isogenic controls into MSNs and carried out quantitative proteomic analysis. Using data-dependent acquisitions with FAIMS for label-free quantification on the Orbitrap Lumos mass spectrometer, we identified 6323 proteins with at least two unique peptides. Of these, 901 proteins were altered significantly more in the HD72-MS2023-01-01T00:00:00Z2023 May2026-07-14T20:07:38.747Z2025-04-06T14:37:29.319ZS-EPMC101654593695862710.1016/j.mcpro.2023.100534