TY - JOUR
T1 - Brain, blood, and iron
T2 - Perspectives on the roles of erythrocytes and iron in neurodegeneration
AU - Prohaska, Rainer
AU - Sibon, Ody C.M.
AU - Rudnicki, Dobrila D.
AU - Danek, Adrian
AU - Hayflick, Susan J.
AU - Verhaag, Esther M.
AU - Vonk, Jan J.
AU - Margolis, Russell L.
AU - Walker, Ruth H.
N1 - Funding Information:
This article reflects presentations and discussion at a meeting entitled “Brain, Blood and Iron: Joint International Symposium on Neuroacanthocytosis and Neurodegeneration with Brain Iron Accumulation” which was held in Bethesda, MD, USA on Oct 1–2 2010. This meeting was supported by the National Institute of Neurological Diseases and Stroke; the Office of Rare Diseases Research, and the National Institute of Child Health and Human Development [1R13NS067922-01], and also by the Movement Disorder Society, Advocacy for Neuroacanthocytosis Patients (UK), Associazione Italiana Sindromi Neurodegenerative da Accumulo di Ferro (AISNAF) (Italy), NBIA Disorders Association (USA), Hoffnungsbaum e.V. (Germany) and GlaxoSmithKline. Funding by an ERA-Net E-Rare project, “European Multidisciplinary Initiative on Neuroacanthocytosis (EMINA)”, is gratefully acknowledged by AD (BMBF/DLR grant 01GM1003), RP (FWF grant I 438-B13), and OCMS (ZonMW grant 113301162).
PY - 2012/6
Y1 - 2012/6
N2 - The terms "neuroacanthocytosis" (NA) and "neurodegeneration with brain iron accumulation" (NBIA) both refer to groups of genetically heterogeneous disorders, classified together due to similarities of their phenotypic or pathological findings. Even collectively, the disorders that comprise these sets are exceedingly rare and challenging to study. The NBIA disorders are defined by their appearance on brain magnetic resonance imaging, with iron deposition in the basal ganglia. Clinical features vary, but most include a movement disorder. New causative genes are being rapidly identified; however, the mechanisms by which mutations cause iron accumulation and neurodegeneration are not well understood. NA syndromes are also characterized by a progressive movement disorder, accompanied by cognitive and psychiatric features, resulting from mutations in a number of genes whose roles are also basically unknown. An overlapping feature of the two groups, NBIA and NA, is the occurrence of acanthocytes, spiky red cells with a poorly-understood membrane dysfunction. In this review we summarise recent developments in this field, specifically insights into cellular mechanisms and from animal models. Cell membrane research may shed light upon the significance of the erythrocyte abnormality, and upon possible connections between the two sets of disorders. Shared pathophysiologic mechanisms may lead to progress in the understanding of other types of neurodegeneration.
AB - The terms "neuroacanthocytosis" (NA) and "neurodegeneration with brain iron accumulation" (NBIA) both refer to groups of genetically heterogeneous disorders, classified together due to similarities of their phenotypic or pathological findings. Even collectively, the disorders that comprise these sets are exceedingly rare and challenging to study. The NBIA disorders are defined by their appearance on brain magnetic resonance imaging, with iron deposition in the basal ganglia. Clinical features vary, but most include a movement disorder. New causative genes are being rapidly identified; however, the mechanisms by which mutations cause iron accumulation and neurodegeneration are not well understood. NA syndromes are also characterized by a progressive movement disorder, accompanied by cognitive and psychiatric features, resulting from mutations in a number of genes whose roles are also basically unknown. An overlapping feature of the two groups, NBIA and NA, is the occurrence of acanthocytes, spiky red cells with a poorly-understood membrane dysfunction. In this review we summarise recent developments in this field, specifically insights into cellular mechanisms and from animal models. Cell membrane research may shed light upon the significance of the erythrocyte abnormality, and upon possible connections between the two sets of disorders. Shared pathophysiologic mechanisms may lead to progress in the understanding of other types of neurodegeneration.
KW - Iron
KW - NBIA
KW - Neuroacanthocytosis
KW - Neurodegeneration
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U2 - 10.1016/j.nbd.2012.03.006
DO - 10.1016/j.nbd.2012.03.006
M3 - Review article
C2 - 22426390
AN - SCOPUS:84860834207
SN - 0969-9961
VL - 46
SP - 607
EP - 624
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 3
ER -