Imaging neuronal loss and recovery in compromised but viable brain tissue.

basic disease mechanism has also recently been implicated in a novel form of hereditary spastic paraparesis due to mutations in another beta-propeller protein, tectonin beta-propeller repeat-con-taning 2, TECPR2 (Oz-Levi et al., 2012). However it is still unclear how increased autophagy relates to iron accumulation. Various basic mechanisms have been implicated in NBIA (altered iron metabolism , fatty acid metabolism, apoptosis, transcriptional regulation , autophagy), but whether abnormal iron deposition is a final common pathway, directly leading to disturbed neuronal dysfunc-tion, or a 'biomarker' of NBIA, facilitating disease detection remains to be established (Fig. 1). Identification of novel genetic forms of NBIA, such as the recently reported BPAN provides novel insights to answer this very important question. Better understanding of the disease mechanisms and their role in iron accumulation is essential to define whether novel therapeutic interventions should target iron deposition, or the primary defect (autophagy, fatty acid metabolism, apoptosis etc), secondarily leading to iron deposition, or both (Fig. 1). In neuroferritinopathy, signal intensity in the thalamus showed documented changes over time and good correlation with the clinical rating scale measuring dystonia severity, establishing a link between iron accumulation and clinical presentation (McNeil et al., 2012). Similar studies are urgently needed in other NBIA conditions to determine the natural history of disease and to provide the platform for therapeutic intervention. et al. Exome sequencing reveals de novo WDR45 mutations causing a phenotypically distinct, X-linked dominant form of NBIA. Absence of an orphan mitochondrial protein, C19orf12, causes a distinct clinical subtype of neurodegeneration with brain iron accumulation. et al. Beta-propeller protein-associated neurodegeneration: a new X-linked dominant disorder with brain iron accumulation. A new phenotype of brain iron accumulation with dystonia, optic atrophy, and peripheral neuropathy. Progressive brain iron accumulation in neuroferritinopathy measured by the thalamic T2* relaxation rate. et al. PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron. et al. De novo mutations in the autophagy gene WDR45 cause static encephalopathy of childhood with neurodegeneration in adult-Selective neuronal loss, that is necrosis or apoptosis of a portion of neurons in cerebral tissue with grossly preserved architecture (Garcia et al., 1996), is difficult to assess but can seriously impact brain function in patients with cerebrovascular disease. It has been associated with temporary cerebral ischaemia, as in reperfused penumbral tissue (Garcia et al., 1996; Baron, 2005), and with chronic cerebral hypoperfusion due, for example, to atheroscler-otic disease of …