TY - JOUR
T1 - PNPLA6/NTE, an Evolutionary Conserved Phospholipase Linked to a Group of Complex Human Diseases
AU - Kretzschmar, Doris
N1 - Funding Information:
Funding: This research was funded by the National Institute of Health (RO1NS047663) to D.K.
Publisher Copyright:
© 2022 by the author. Licensee MDPI, Basel, Switzerland.
PY - 2022/4
Y1 - 2022/4
N2 - Patatin-like phospholipase domain-containing protein 6 (PNPLA6), originally called Neuropathy Target Esterase (NTE), belongs to a family of hydrolases with at least eight members in mammals. PNPLA6/NTE was first identified as a key factor in Organophosphate-induced delayed neuropathy, a degenerative syndrome that occurs after exposure to organophosphates found in pesticides and nerve agents. More recently, mutations in PNPLA6/NTE have been linked with a number of inherited diseases with diverse clinical symptoms that include spastic paraplegia, ataxia, and chorioretinal dystrophy. A conditional knockout of PNPLA6/NTE in the mouse brain results in age-related neurodegeneration, whereas a complete knockout causes lethality during embryogenesis due to defects in the development of the placenta. PNPLA6/NTE is an evolutionarily conserved protein that in Drosophila is called Swiss-Cheese (SWS). Loss of SWS in the fly also leads to locomotory defects and neuronal degeneration that progressively worsen with age. This review will describe the identification of PNPLA6/NTE, its expression pattern, and normal role in lipid homeostasis, as well as the consequences of altered NPLA6/NTE function in both model systems and patients.
AB - Patatin-like phospholipase domain-containing protein 6 (PNPLA6), originally called Neuropathy Target Esterase (NTE), belongs to a family of hydrolases with at least eight members in mammals. PNPLA6/NTE was first identified as a key factor in Organophosphate-induced delayed neuropathy, a degenerative syndrome that occurs after exposure to organophosphates found in pesticides and nerve agents. More recently, mutations in PNPLA6/NTE have been linked with a number of inherited diseases with diverse clinical symptoms that include spastic paraplegia, ataxia, and chorioretinal dystrophy. A conditional knockout of PNPLA6/NTE in the mouse brain results in age-related neurodegeneration, whereas a complete knockout causes lethality during embryogenesis due to defects in the development of the placenta. PNPLA6/NTE is an evolutionarily conserved protein that in Drosophila is called Swiss-Cheese (SWS). Loss of SWS in the fly also leads to locomotory defects and neuronal degeneration that progressively worsen with age. This review will describe the identification of PNPLA6/NTE, its expression pattern, and normal role in lipid homeostasis, as well as the consequences of altered NPLA6/NTE function in both model systems and patients.
KW - Neuropathy Target Esterase
KW - Protein kinase A
KW - Swiss-Cheese
KW - hereditary spastic paraplegia
KW - organophosphate-induced delayed neuropathy
KW - phosphatidylcholine
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U2 - 10.3390/metabo12040284
DO - 10.3390/metabo12040284
M3 - Review article
AN - SCOPUS:85127669308
VL - 12
JO - Metabolites
JF - Metabolites
SN - 2218-1989
IS - 4
M1 - 284
ER -