Pantothenate Rescues Iron Accumulation in Pantothenate Kinase-Associated Neurodegeneration Depending on the Type of Mutation

Molecular Neurobiology
Mónica Álvarez-CórdobaJosé A Sánchez-Alcázar

Abstract

Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurologic disorders in which iron accumulates in the basal ganglia resulting in progressive dystonia, spasticity, parkinsonism, neuropsychiatric abnormalities, and optic atrophy or retinal degeneration. The most prevalent form of NBIA is pantothenate kinase-associated neurodegeneration (PKAN) associated with mutations in the gene of pantothenate kinase 2 (PANK2), which is essential for coenzyme A (CoA) synthesis. There is no cure for NBIA nor is there a standard course of treatment. In the current work, we describe that fibroblasts derived from patients harbouring PANK2 mutations can reproduce many of the cellular pathological alterations found in the disease, such as intracellular iron and lipofuscin accumulation, increased oxidative stress, and mitochondrial dysfunction. Furthermore, mutant fibroblasts showed a characteristic senescent morphology. Treatment with pantothenate, the PANK2 enzyme substrate, was able to correct all pathological alterations in responder mutant fibroblasts with residual PANK2 enzyme expression. However, pantothenate had no effect on mutant fibroblasts with truncated/incomplete protein expression. The positive effect of pa...Continue Reading

References

Aug 1, 1985·Experimental Eye Research·M Boulton, J Marshall
Nov 5, 1997·Nature Biotechnology·R ZuffereyD Trono
Sep 5, 2002·Free Radical Biology & Medicine·Ulf T Brunk, Alexei Terman
Jan 3, 2003·The New England Journal of Medicine·Susan J HayflickJane Gitschier
Jul 22, 2004·Analytical Biochemistry·Jan RiemerRalf Dringen
Nov 5, 2004·Human Molecular Genetics·Yien-Ming KuoJane Gitschier
May 17, 2005·Progress in Lipid Research·Roberta LeonardiSuzanne Jackowski
Sep 28, 2006·Investigative Ophthalmology & Visual Science·Almut Bindewald-WittichFrank G Holz
Sep 11, 2007·FEBS Letters·Roberta LeonardiSuzanne Jackowski
Dec 7, 2007·Annals of the New York Academy of Sciences·Tobias JungTilman Grune
Feb 8, 2008·Biochimica Et Biophysica Acta·Tino KurzUlf T Brunk
Feb 19, 2008·Cellular and Molecular Life Sciences : CMLS·K L DoubleU T Brunk
Nov 5, 2008·Journal of Medical Genetics·A GregoryS J Hayflick
Mar 31, 2010·Proceedings of the National Academy of Sciences of the United States of America·Anil RanaOdy C M Sibon
Jul 8, 2010·Bioorganic & Medicinal Chemistry Letters·Kosei ShiojiHiroyuki Nakagawa
Jan 15, 2011·International Journal of Alzheimer's Disease·Gabriela A SalvadorNorma M Giusto
Feb 19, 2011·Micron : the International Research and Review Journal for Microscopy·Antje BiesemeierOliver Eibl
May 7, 2011·Antioxidants & Redox Signaling·Michael Li-Hsuan HuangDes R Richardson
Feb 10, 2012·Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine·Marco T NúñezJulio Salazar
Jan 15, 2013·Current Protocols in Human Genetics·Ivan AdzhubeiShamil R Sunyaev
Sep 12, 2013·Redox Biology·Annika Höhn, Tilman Grune
Nov 12, 2013·International Review of Neurobiology·Michael C Kruer
May 23, 2014·Frontiers in Pharmacology·Sonia Levi, Dario Finazzi
Sep 3, 2014·Antioxidants & Redox Signaling·Sandra Reeg, Tilman Grune
Dec 3, 2014·Current Opinion in Microbiology·Roland LillUlrich Mühlenhoff
Aug 26, 2015·Journal of Laboratory Automation·Mario Rodríguez-ArribasJosé M Fuentes
Apr 1, 2007·EcoSal Plus·Roberta Leonardi, Suzanne Jackowski

❮ Previous
Next ❯

Citations

Feb 26, 2019·Neural Regeneration Research·Mónica Alvarez-CordobaJosé A Sánchez-Alcázar
Jun 18, 2019·Journal of Experimental Neuroscience·Suzanne Jackowski
Apr 25, 2020·Antioxidants·Carmen EspinósFederico V Pallardó
Jan 6, 2021·International Journal of Molecular Sciences·Camilla Ceccatelli BertiPaola Goffrini
Nov 19, 2020·Diseases·Irene Villalón-GarcíaJosé Antonio Sánchez-Alcázar
Jan 10, 2020·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Chitra SubramanianSuzanne Jackowski
May 4, 2021·Frontiers in Neurology·Vassilena IankovaSusanne A Schneider
May 2, 2021·Brain Research Bulletin·Zhiwen GengBernard Yan
May 19, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Nivedita ThakurHyder A Jinnah
Aug 28, 2021·Brain Sciences·Luca MignaniDario Finazzi

❮ Previous
Next ❯

Methods Mentioned

BETA
light microscopy
fluorescence microscopy
Scanning
X-ray
Fluorescence
Assay
Protein Assay
electron microscopy

Software Mentioned

IFDOTMETER
Originlab
ImageJ
Oxyblot
PolyPhen2
DeltaVision
Origin

Related Concepts

Related Feeds

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.

Basal ganglia in Parkinson's disease (MDS)

The basal ganglia is comprised of the neostriatum, the external and internal pallidal segments, the subthalamic nucleus, the substantia nigra pars reticulata, and the pars compacta of the substantia nigra. The basal ganglia circuitry is responsible for the correct execution of voluntary movements and is implicated in Parkinson's disease. Here is the latest research investigating the basal ganglia in Parkinson's disease.

Batten Disease

Batten Disease is a group of nervous system disorders known as neuronal ceroid lipofuscinosis. This feed focuses on neurobiological and neuropathological aspects of this disease.