Modelling TDP-43 proteinopathy in Drosophila uncovers shared and neuron-specific targets across ALS and FTD relevant circuits

Table 2 Candidate mRNA targets of TDP-43 in mushroom body neurons, identified in Drosophila and found to be transcriptionally altered in single neuronal nuclei from FTD patient brains

Human gene	Fly gene	HGNC ID	DIOPT score	Log2FC	FDR	Gene function	Association with neurodegenerative disease
NFIB	NfI	HGNC:7785	11	0.374332	0.005697	DNA-binding transcription factor activity	Altered expression in AD [127]
PLPPR4	wun	HGNC:23496	3	0.370091	0.000000	Lipid phosphate phosphatase	Altered expression in AD patient cortices [128]
ENC1	dbo	HGNC:3345	4	0.354832	0.000447	Substrate-specific adapter of an E3 ubiquitin-protein ligase complex	Altered expression in AD [108]
TMTC1	Tmtc4	HGNC:24099	3	0.338313	0.006021	Transmembrane O-mannosyltransferase targeting cadherins 4	Altered expression in mouse models of AD [129]
GRIA4	GluRIIE	HGNC:4574	7	0.319357	0.008298	Glutamate receptor	Protein levels reduced across different dementias [130]; altered expression in AD [127]
NCALD	CG5890	HGNC:7655	3	− 0.421750	0.000044	Neuronal calcium sensor	Decreased in AD [131]
FOXP2	FoxP	HGNC:13875	8	− 0.434982	0.002966	Forkhead box transcription factor	Linked to speech and language disorders; downstream targets include motor proteins [132]

DIOPT score—ortholog identifier tool [95]. Log2FC and FDR—differential expression data for human orthologs, identified in neuronal nuclei from FTD patient brains exhibiting the molecular signature of TDP-43 pathology [see Materials and Methods, and 56]. Gene function and association with neurodegenerative disease, as shown. Note: ENC1 and GRIA4 are present on both MB-MN shared and MB unique lists due to homology to distinct genes identified in Drosophila

ISSN: 2051-5960