Brain, blood, and iron: Perspectives on the roles of erythrocytes and iron in neurodegeneration

• Published in: Neurobiology of disease Vol. 46; no. 3; pp. 607 - 624
• Main Authors: Prohaska, Rainer, Sibon, Ody C.M., Rudnicki, Dobrila D., Danek, Adrian, Hayflick, Susan J., Verhaag, Esther M., Vonk, Jan J., Margolis, Russell L., Walker, Ruth H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2012; Elsevier
• Subjects: Animal models; Animals; Autophagy - physiology; Basal ganglia; Blood; Brain; Brain - pathology; Brain Chemistry - physiology; Cell membranes; Cognitive ability; Erythrocytes; Erythrocytes - physiology; Humans; Iron; Iron - blood; Iron - metabolism; Iron - physiology; Magnetic resonance imaging; Movement disorders; Mutation; NBIA; Nervous system; Neuroacanthocytosis; Neuroacanthocytosis - pathology; Neurodegeneration; Neurodegenerative Diseases - blood; Neurodegenerative Diseases - pathology; Neuroimaging; Neurology; NBIA; Iron; Neurodegeneration; Neuroacanthocytosis
• ISSN: 0969-9961; 1095-953X; 1095-953X
• DOI: 10.1016/j.nbd.2012.03.006

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.