Selective degeneration and death of one or more classes of neurons is the defining feature of human neurodegenerative disease. Although traditionally viewed as diseases mainly affecting the most vulnerable neurons, in most instances of inherited disease the causative genes are widely-usually ubiquitously-expressed. Focusing on amyotrophic lateral sclerosis (ALS), especially disease caused by do...

We screened a cohort of 181 patients with features of primary progressive ataxia and chorea for spinocerebellar ataxias 17 (SCA17) mutation after excluding other known SCAs, Huntington's disease (HD), dentatorubral-pallidoluysian atrophy (DRPLA), and non-genetic causes. This study included patients with known family history of SCA, those with sporadic onset and cases of uncertain family history...

Hereditary spastic paraplegias (HSPs) and ataxias are genetically heterogeneous disorders, with more than 70 genes implicated in each group. A smaller fraction of disorders from both groups manifest both with spastic paresis and ataxia, and recognizing this phenotype helps narrowing down the differential diagnosis. Recently, homozygous and compound heterozygous mutations in CAPN1, which encode ...

The IKK/NF-κB signal transduction and transcription factor system is a central regulator of inflammation, cell survival and differentiation, and is implicated in multiple human pathologies including multiple sclerosis, glioblastoma and neurodegenerative disorders. The IKK/NF-κB system is prominently activated by proinflammatory cytokines and molecules derived from pathogens or damaged cells and...

Spinocerebellar ataxia type 2 (SCA2) is among the most common forms of autosomal dominant ataxias, accounting for 15% of the total families. Occurrence is higher in specific populations such as the Cuban and Southern Italian. The disease is caused by a CAG expansion in ATXN2 gene, leading to abnormal accumulation of the mutant protein, ataxin-2, in intracellular inclusions. The clinical picture...

The spinocerebellar ataxias (SCA) are a group of neurodegenerative disorders characterized by heterogeneous clinical presentation. Spinocerebellar ataxia type 7 (SCA7) is caused by an abnormal CAG repeat expansion and includes cerebellar signs associated with visual loss and ophthalmoplegia. Marked anticipation and dynamic mutation is observed in SCA7. Moreover, phenotype variability and very e...

Genetic etiologies of at least 20% of autosomal dominant cerebellar ataxias (ADCAs) have yet to be clarified. We identified a novel spinocerebellar ataxia (SCA) form in four Japanese pedigrees which is caused by an abnormal CAG expansion in the TATA-binding protein (TBP) gene, a general transcription initiation factor. Consequently, it has been added to the group of polyglutamine diseases. This...

Experimental evidence suggests that astrocytes play a crucial role in the physiology of the central nervous system (CNS) by modulating synaptic activity and plasticity. Based on what is currently known we postulate that astrocytes are fundamental, along with neurons, for the information processing that takes place within the CNS. On the other hand, experimental findings and human observations s...

Autosomal dominant spinocerebellar ataxias (SCA) constitute a heterogeneous group of inherited disorders. The transglutaminase 6 (TGM6) gene was recently suggested as a SCA causative gene in Chinese SCA families. In this study, two affected members of a three-generation Chinese family with SCA characterized by progressive cerebellar ataxia and lower limb pyramidal signs were subjected to whole ...

Cerebellar ataxias are a group of progressive, debilitating diseases often associated with abnormal Purkinje cell (PC) firing and/or degeneration. Many animal models of cerebellar ataxia display abnormalities in Ca²⁺ channel function. The 'ducky' du(2J) mouse model of ataxia and absence epilepsy represents a clean knock-out of the auxiliary Ca²⁺ channel subunit α2δ-2, and has been associated wi...