Overexpression of Human Mutant PANK2 Proteins Affects Development and Motor Behavior of Zebrafish Embryos.

Neuromolecular Medicine
Deepak KhatriDario Finazzi

Abstract

Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a genetic and early-onset neurodegenerative disorder characterized by iron accumulation in the basal ganglia. It is due to mutations in Pantothenate Kinase 2 (PANK2), an enzyme that catalyzes the phosphorylation of vitamin B5, first and essential step in coenzyme A (CoA) biosynthesis. Most likely, an unbalance of the neuronal levels of this important cofactor represents the initial trigger of the neurodegenerative process, yet a complete understanding of the connection between PANK2 malfunctioning and neuronal death is lacking. Most PKAN patients carry mutations in both alleles and a loss of function mechanism is proposed to explain the pathology. When PANK2 mutants were analyzed for stability, dimerization capacity, and enzymatic activity in vitro, many of them showed properties like the wild-type form. To further explore this aspect, we overexpressed the wild-type protein, two mutant forms with reduced kinase activity and two retaining the catalytic activity in zebrafish embryos and analyzed the morpho-functional consequences. While the wild-type protein had no effects, all mutant proteins generated phenotypes that partially resembled those observed in pank2 and coasy...Continue Reading

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Citations

Mar 29, 2019·Biomedicines·Ram Manohar BasnetMaurizio Memo
Nov 26, 2020·Bulletin of Experimental Biology and Medicine·D KhatriD Finazzi
Jan 12, 2021·Frontiers in Cell and Developmental Biology·Luca MignaniDario Finazzi
Jan 6, 2021·International Journal of Molecular Sciences·Camilla Ceccatelli BertiPaola Goffrini
Aug 28, 2021·Brain Sciences·Luca MignaniDario Finazzi

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Methods Mentioned

BETA
transgenic
in vitro transcription
PCR

Software Mentioned

- Time PCR Tool
LAS Leica Imaging
ImageJ
IDT
Real

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