Article

Small molecules targeting ARF1 interaction with C9orf72:SMCR8:WDR41 complexes suppress its overactivation implicated in ALS/FTD

2026-01-27

Abstract excerpt

The hexanucleotide repeat expansion in C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS)/frontotemporal dementia (FTD). The C9orf72 protein forms a complex with SMCR8 and WDR41 (CSW), which functions as a GTPase-activating protein (GAP) regulating ARF1 and RAB small GTPases. While these findings implicated ARF1-GAP dysregulation in ALS/FTD and supported ARF1 suppression as poten...

Topics

Open a Topic to create a Post that cites this publication.

Identifiers and source

Literature Corpus work: 42fde934-f80d-590e-a28e-8b351dbcf3f4
DOI: 10.64898/2026.01.24.701325

Open publication

Related research

Semantic proximity does not establish scientific evidence.

Click a neighbor to travelStep 1 · 12 closest

Small molecules targeting ARF1 interaction with C9orf72:SMCR8:WDR41 complexes suppress its overactivation implicated in ALS/FTDDOI 10.64898/2026.01.24.701325Read

Structure of the C9orf72 ARF GAP complex that is haploinsufficient in ALS and FTD.Semantic proximity Read

C9orf72’s Interaction with Rab GTPases—Modulation of Membrane Traffic and AutophagySemantic proximity Read

ALS-linked C9orf72–SMCR8 complex is a negative regulator of primary ciliogenesisSemantic proximity Read

C9orf72, a protein associated with amyotrophic lateral sclerosis (ALS) is a guanine nucleotide exchange factorSemantic proximity Read

C9orf72 and RAB7L1 regulate vesicle trafficking in amyotrophic lateral sclerosis and frontotemporal dementiaSemantic proximity Read

Cellular and physiological functions of C9ORF72 and implications for ALS/FTD.Semantic proximity Read

A C9ORF72/SMCR8-containing complex regulates ULK1 and plays a dual role in autophagySemantic proximity Read

The ALS/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathwaySemantic proximity Read

Ftd/Als Type 7–Associated Thr104Asn Mutation of CHMP2B Blunts Neuronal Process Elongation, and Is Recovered by Knockdown of Arf4, the Golgi Stress Regulator, in N1E-115 CellsSemantic proximity Read

Structure of the human C9orf72-SMCR8 complex reveals a multivalent protein interaction architectureSemantic proximity Read

C9orf72 binds SMCR8, localizes to lysosomes, and regulates mTORC1 signaling.Semantic proximity Read