Skip to main content

Table 3 Loss of NCL protein function in mammals and the effects on the expression, amounts, and activities of NCL genes/proteins

From: Molecular networking in the neuronal ceroid lipofuscinoses: insights from mammalian models and the social amoeba Dictyostelium discoideum

Loss of PPT1/CLN1 function Sample Affected gene/protein Reference
Ppt1/Cln1−/− Brain tissues and cells from a Ppt1/Cln1−/− mouse Increased expression of CtsD/Cln10 Chandra et al., 2015 [87]
Ppt1/Cln1−/− Brain tissues and cells from a Ppt1/Cln1−/− mouse Reduced maturation of CTSD/CLN10 to its enzymatically active form Chandra et al., 2015 [87]
Loss of TPP1/CLN2 function Sample Affected gene/protein Reference
Tpp1/Cln2−/− Brain tissues from a Tpp1/Cln2−/− mouse Increased expression of CtsD/Cln10 Domowicz et al., 2019 [88]
Tpp1/Cln2−/− Brain tissues from a Tpp1/Cln2−/− mouse Increased expression of Pgrn/Cln11 Domowicz et al., 2019 [88]
Loss of CLN3 function Sample Affected gene/protein Reference
CLN3 (mutated) CLN3 disease patient fibroblasts Reduced amount of PPT1/CLN1 in lysosomes, which correlated with reduced enzymatic activity Appu et al., 2019 [89]
Cln3Δex7/8 Mouse brain cortex from a Cln3Δex7/8 mouse Reduced amount of PPT1/CLN1 in lysosomes, which correlated with reduced enzymatic activity Appu et al., 2019 [89]
Cln3Δex7/8 Cerebellar cells from a Cln3Δex7/8 mouse Increased amount of PPT1/CLN1 in lysosomes, which correlated with increased enzymatic activity Schmidtke et al., 2019 [90]
Cln3Δex7/8 Cerebellar cells from a Cln3Δex7/8 mouse Increased amount of TPP1/CLN2 in lysosomes Schmidtke et al., 2019 [90]
Cln3Δex7/8 Cerebellar cells from a Cln3Δex7/8 mouse Decreased amount of CLN5 in lysosomes Schmidtke et al., 2019 [90]
Cln3Δex7/8 Cerebellar cells from a Cln3Δex7/8 mouse Decreased amount of CTSD/CLN10 in lysosomes Schmidtke et al., 2019 [90]
Loss of DNAJC5/CLN4 function Sample Affected gene/protein Reference
DNAJC5/CLN4 (mutated) CLN4 disease patient brain Increased amount of PPT1/CLN1 Henderson et al., 2016 [81]
DNAJC5/CLN4 (mutated) CLN4 disease patient brain Reduced enzymatic activity of PPT1/CLN1, which resulted in its mis-localization Henderson et al., 2016 [81]
Loss of CLN5 function Sample Affected gene/protein Reference
CLN5 (mutated) CLN5 disease patient fibroblasts Increased activity of TPP1/CLN2 Vesa et al., 2002 [77]
Loss of MFSD8/CLN7 function Sample Affected gene/protein Reference
Mfsd8/Cln7−/− Embryonic fibroblasts from a Mfsd8/Cln7−/− mouse Reduced amount of CLN5 in lysosomes Danyukova et al., 2018 [91]
Loss of PGRN/CLN11 function Sample Affected gene/protein Reference
PGRN/CLN11 (heterozygous mutation) FTD patient fibroblasts Reduced activity of CTSD/CLN10 Ward et al., 2017 [92]
PGRN/CLN11 (heterozygous mutation) FTD patient iPSC-derived cortical neurons Reduced activity of CTSD/CLN10 Valdez et al., 2017 [80]
PGRN/CLN11−/− Liver, spleen, and brain samples from a PGRN/CLN11−/−mouse Reduced activity of CTSD/CLN10 Zhou et al., 2017 [79]
Loss of ATP13A2/CLN12 function Sample Affected gene/protein Reference
ATP13A2/CLN12 knockdown SH-SY5Y human neuroblastoma cells Reduced amount and activity of CTSD/CLN10 Matsui et al., 2013 [93]