Genetics and Pathophysiology of Neurodegeneration with Brain Iron Accumulation (NBIA)
Identifieur interne : 000120 ( Main/Exploration ); précédent : 000119; suivant : 000121Genetics and Pathophysiology of Neurodegeneration with Brain Iron Accumulation (NBIA)
Auteurs : Susanne. Schneider [Allemagne, Royaume-Uni] ; Petr Dusek [République tchèque] ; John Hardy [Royaume-Uni] ; Ana Westenberger [Allemagne] ; Joseph Jankovic [États-Unis] ; Kailash. Bhatia [Royaume-Uni]Source :
- Current Neuropharmacology [ 1570-159X ] ; 2013.
Abstract
Our understanding of the syndromes of Neurodegeneration with Brain Iron Accumulation (NBIA) continues to grow considerably. In addition to the core syndromes of pantothenate kinase-associated neurodegeneration (PKAN, NBIA1) and PLA2G6-associated neurodegeneration (PLAN, NBIA2), several other genetic causes have been identified (including FA2H, C19orf12, ATP13A2, CP and FTL). In parallel, the clinical and pathological spectrum has broadened and new age-dependent presentations are being described. There is also growing recognition of overlap between the different NBIA disorders and other diseases including spastic paraplegias, leukodystrophies and neuronal ceroid lipofuscinosis which makes a diagnosis solely based on clinical findings challenging. Autopsy examination of genetically-confirmed cases demonstrates Lewy bodies, neurofibrillary tangles, and other hallmarks of apparently distinct neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer’s disease. Until we disentangle the various NBIA genes and their related pathways and move towards pathogenesis-targeted therapies, the treatment remains symptomatic.
Our aim here is to provide an overview of historical developments of research into iron metabolism and its relevance in neurodegenerative disorders. We then focus on clinical features and investigational findings in NBIA and summarize therapeutic results reviewing reports of iron chelation therapy and deep brain stimulation. We also discuss genetic and molecular underpinnings of the NBIA syndromes.
Url:
DOI: 10.2174/157015913804999469
PubMed: 23814539
PubMed Central: 3580793
Affiliations:
- Allemagne, Royaume-Uni, République tchèque, États-Unis
- Angleterre, Bohême centrale, Schleswig-Holstein, Texas
- Houston, Kiel, Prague
- Baylor College of Medicine
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Le document en format XML
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<front><div type="abstract" xml:lang="en"><p>Our understanding of the syndromes of Neurodegeneration with Brain Iron Accumulation (NBIA) continues to grow considerably. In addition to the core syndromes of pantothenate kinase-associated neurodegeneration (PKAN, NBIA1) and PLA2G6-associated neurodegeneration (PLAN, NBIA2), several other genetic causes have been identified (including FA2H, C19orf12, ATP13A2, CP and FTL). In parallel, the clinical and pathological spectrum has broadened and new age-dependent presentations are being described. There is also growing recognition of overlap between the different NBIA disorders and other diseases including spastic paraplegias, leukodystrophies and neuronal ceroid lipofuscinosis which makes a diagnosis solely based on clinical findings challenging. Autopsy examination of genetically-confirmed cases demonstrates Lewy bodies, neurofibrillary tangles, and other hallmarks of apparently distinct neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer’s disease. Until we disentangle the various NBIA genes and their related pathways and move towards pathogenesis-targeted therapies, the treatment remains symptomatic. </p>
<p>Our aim here is to provide an overview of historical developments of research into iron metabolism and its relevance in neurodegenerative disorders. We then focus on clinical features and investigational findings in NBIA and summarize therapeutic results reviewing reports of iron chelation therapy and deep brain stimulation. We also discuss genetic and molecular underpinnings of the NBIA syndromes.</p>
</div>
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<author><name sortKey=" Baltuch, G H" uniqKey=" Baltuch G">G H Baltuch</name>
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<author><name sortKey=" Vercueil, L" uniqKey=" Vercueil L">L Vercueil</name>
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<li>Royaume-Uni</li>
<li>République tchèque</li>
<li>États-Unis</li>
</country>
<region><li>Angleterre</li>
<li>Bohême centrale</li>
<li>Schleswig-Holstein</li>
<li>Texas</li>
</region>
<settlement><li>Houston</li>
<li>Kiel</li>
<li>Prague</li>
</settlement>
<orgName><li>Baylor College of Medicine</li>
</orgName>
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<name sortKey="Bhatia, Kailash P" sort="Bhatia, Kailash P" uniqKey="Bhatia K" first="Kailash" last="Bhatia">Kailash. Bhatia</name>
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<country name="République tchèque"><region name="Bohême centrale"><name sortKey="Dusek, Petr" sort="Dusek, Petr" uniqKey="Dusek P" first="Petr" last="Dusek">Petr Dusek</name>
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