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Proteomic profiling of the global protein changes of Neuro-2a cells treated with dFUS-E9C or control

ABSTRACT: We conducted unbiased mass spectrometric experiments to evaluate the specificity of dFUS-E9C. In these studies, Neuro-2a cells were treated with dFUS-E9C. The result revealed the detection of more than 5000 proteins, among which there was a notable degradation of FUS, confirming the targeted action of dFUS-E9C against FUS protein.

ORGANISM(S): Mus Musculus

SUBMITTER: Songbo Xie

PROVIDER: PXD062671 | iProX | Fri Apr 04 00:00:00 BST 2025

REPOSITORIES: iProX

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DNA nanoflower Oligo-PROTAC for targeted degradation of FUS to treat neurodegenerative diseases.

Ge Ruixin R Chen Miao M Wu Sijin S Huang Sirui S Zhou Ping P Cao Minghui M Zhang Fan F Zang Jinzhi J Zhu Yigao Y Li Jingrui J Ni Guilin G Yang Zhihao Z Li Qingchao Q Pan Wei W Zhang Liang L Liu Min M Xuan Chenghao C Yu Haiyang H Zhou Jun J Xie Songbo S

Nature communications 20250520 1

Oligonucleotide-based medicine faces challenges in efficiently crossing the blood-brain barrier and rapidly reducing toxic proteins. To address these challenges, here we establish an integrated modality, brain-penetrant DNA nanoflowers incorporated with oligonucleotide-based proteolysis targeting chimeras. Using FUS as a proof-of-concept, mutations of which cause frontotemporal dementia and amyotrophic lateral sclerosis, we demonstrate that a FUS-engaging RNA oligonucleotide crosslinked to a lig ...[more]

PMID: 40394046

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