BACKGROUND Pantothenate kinase-associated neurodegeneration, PKAN, is an inherited disorder characterized by progressive impairment in motor coordination and caused by mutations in PANK2, a human gene that encodes one of four pantothenate kinase (PanK) isoforms. PanK initiates the synthesis of coenzyme A (CoA), an essential cofactor that plays a key role in energy metabolism and lipid synthesis...

Human neuronal ceroid lipofuscinoses (NCLs) are a group of genetic neurodegenerative diseases characterized by progressive death of neurons in the central nervous system (CNS) and accumulation of abnormal lysosomal storage material. Infantile NCL (INCL), the most severe form of NCL, is caused by mutations in the Ppt1 gene, which encodes the lysosomal enzyme palmitoyl-protein thioesterase 1 (Ppt...

We have previously shown that a quantitative-trait locus linked to the OCA2 region of 15q accounts for 74% of variation in human eye color. We conducted additional genotyping to clarify the role of the OCA2 locus in the inheritance of eye color and other pigmentary traits associated with skin-cancer risk in white populations. Fifty-eight synonymous and nonsynonymous exonic single-nucleotide pol...

Inflammation is associated with many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. In this Review, we discuss inducers, sensors, transducers, and effectors of neuroinflammation that contribute to neuronal dysfunction and death. Although inducers of inflammation may be generated in a disease-specific manner,...

The familial disease of the cerebral white matter named after Krabbe (1916) may be distinguished histologically from other leucoencephalopathies of early life by the presence of conspicuous nests of macrophage cells, some of large size with several peripherally placed nuclei, lying closely packed around the smaller vessels of the cerebral white matter. The large multinucleated cells were design...

ABSTARCT Hallervorden-Spatz disease (HSD) is a rare disorder characterized by progressive motor dysfunction and dementia. Dystonia is the most prominent and disabling symptom responding only to a modest extent to pharmacological therapy. At the moment only a few cases have been reported to improve dystonia and even fewer to resolve status dystonicus for a longer period in children. The authors ...

THE phenomenon of hypermyelinization has received much attention from neuropathologists since C. Vogt's (1911) original description of status marmoratus of the corpus striatum. It is now well established that hypermyelinized fibres in the form of plaques or as the peculiar networks which first suggested the name " marbled " may be present in many parts of the nervous system, though they are mos...

Degenerative diseases of the central nervous system have until recently been considered as being rather fixed in type, and most cases could be readily classified. The outstanding degenerative diseases are: Amyotrophic Lateral Sclerosis, Spinal Muscular Atrophy, and Friedreich's Tabes in the spinal cord. In the encephalon they are: Atrophy of either basal ganglia or the cerebellum, together with...

Pantothenate kinase-associated neurodegeneration is an early onset autosomal recessive movement disorder caused by mutation of the pantothenate kinase-2 gene, which encodes a mitochondrial enzyme involved in coenzyme A synthesis. The disorder is characterised by high iron levels in the brain, although the pathological mechanism leading to this accumulation is unknown. To address this question, ...

Parkinson's disease (PD)-mimicking drugs and pesticides, and more recently PD-associated gene mutations, have been studied in cell cultures and mammalian models to decipher the molecular basis of PD. Thus far, a dozen of genes have been identified that are responsible for inherited PD. However they only account for about 8% of PD cases, most of the cases likely involving environmental contribut...