Abnormal red cells features associated with hereditary neurodegenerative disorders: the neuroacanthocytosis syndromes.

Purpose of reviewThis review discusses the mechanisms involved in the generation of thorny red blood cells (RBCs), known asacanthocytes, in patients with neuroacanthocytosis, a heterogenous group of neurodegenerative hereditarydisorders that include chorea-acanthocytosis (ChAc) and McLeod syndrome (MLS).Recent findingsAlthough molecular defects associated with neuroacanthocytosis have been identified recently, theirpathophysiology and the related RBC abnormalities are largely unknown. Studies in ChAc RBCs haveshown an altered association between the cytoskeleton and the integral membrane protein compartment inthe absence of major changes in RBC membrane composition. In ChAc RBCs, abnormal Lyn kinaseactivation in a Syk-independent fashion has been reported recently, resulting in increased band 3 tyrosinephosphorylation and perturbation of the stability of the multiprotein band 3-based complexes bridging themembrane to the spectrin-based membrane skeleton. Similarly, in MLS, the absence of XK-protein, which isassociated with the spectrin–actin–4.1 junctional complex, is associated with an abnormal membraneprotein phosphorylation state, with destabilization of the membrane skeletal network resulting in generationof acanthocytes.SummaryA novel mechanism in generation of acanthocytes involving abnormal Lyn activation, identified in ChAc,expands the acanthocytosis phenomenon toward protein–protein interactions, controlled byphosphorylation-related abnormal signaling.