Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153640 (Cerebellum)
 1,777 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant spinocerebellar degeneration characterized by a wide range of clinical manifestations. In this review, we discuss the role(s) that heat shock protein 27 (HSP27) may play in the cell death process of spinocerebellar ataxia type 3.
Cerebellum 2005
PMID:HSP27 and cell death in spinocerebellar ataxia type 3. 1589 56

Spinocerebellar ataxia type 10 (SCA10) is a dominantly inherited ataxia caused by expansion of ATTCT pentanucleotide repeat in intron 9 of a novel gene, E46L, on chromosome 22q13.3. SCA10 is a complex neurodegenerative condition. Initial studies characterized SCA10 as pure cerebellar ataxia associated with seizures. Recent identification of new SCA10 families revealed more diverse phenotypes, including polyneuropathy, pyramidal signs, cognitive and neuropsychiatric impairment. Moreover, several families manifest with ataxia without seizures. Thus a complete clinical spectrum is emerging. Progress has also been made in understanding the molecular and genetic mechanisms of pathogenesis. The length of expanded ATTCT repeats is variable in different tissues and highly unstable during paternal transmission, revealing complex genetic and pathogenetic processes. Under torsional stress, ATTCT repeats form unpaired DNA structure and may serve as an erroneous DNA replication origin, potentially contributing to repeat instability and aberrant cell cycle entry. E46L is a cytoplasmic protein with unknown function. Reduced expression of E46L in primary neuronal cultures from cerebellum and cortex by small interfering RNAs (siRNAs) caused increased apoptosis, raising the possibility that reduced expression of E46L might also play an important role in SCA10 pathogenesis.
Cerebellum 2005
PMID:Recent progress in spinocerebellar ataxia type-10 (SCA10). 1589 57

Spinocerebellar ataxia 13 is a slowly progressive and relatively pure autosomal dominant cerebellar ataxia with childhood onset and mental deficiency. The responsible gene has been assigned to a 5.2 Mbases interval on chromosome 19q in a single French family.
Cerebellum 2005
PMID:Spinocerebellar ataxia with mental retardation (SCA13). 1589 58

Spinocerebellar ataxia type 15 (SCA15) was first reported in 2001 on the basis of a single large Anglo-Celtic family from Australia, the locus mapping to chromosomal region 3p24.2-3pter. The characteristic clinical feature was of very slow progression, with two affected individuals remaining ambulant without aids after over 50 years of symptoms. Head and/or upper limb action tremor, and gaze-evoked horizontal nystagmus were seen in several persons. MRI brain scans showed predominant vermal atrophy, sparing the brainstem. In 2004, a Japanese pedigree was reported, which displayed very similar clinical features to the original SCA15 family, and which mapped to an overlapping candidate region. These two families might plausibly reflect a locus homogeneity, but for the present this remains an open question.
Cerebellum 2005
PMID:Spinocerebellar ataxia type 15. 1589 59

Spinocerebellar ataxia type 20 (SCA20) was reported in 2004 in a single Australian Anglo-Celtic pedigree. The phenotype is distinctive, with palatal tremor, and hypermetric saccades, and early dentate (but not pallidal) calcification in the absence of abnormalities of calcium metabolism. Dysarthria, rather than gait ataxia, was the initial symptom in most, and was typically conjoined with dysphonia, clinically resembling adductor spasmodic dysphonia. The onset of these speech abnormalities was abrupt in some cases. MRI scanning showed mild to moderate pancerebellar atrophy with dentate calcification, with olivary pseudohypertrophy in some cases, in the absence of other brainstem or cerebral changes. Nerve conduction studies were normal. Progression appeared to be slow. SCA20 is probably rare, as despite the distinctive phenotype, only this one pedigree has been described. The locus mapped to the pericentromeric region of chromosome 11 with a LOD score of 4.47, and its candidate region overlaps that of SCA5. It seems probable that these two SCAs may be separate genetic entities, on the basis of their divergent clinical features, but formal proof awaits discovery of one or both responsible genes.
Cerebellum 2005
PMID:Spinocerebellar ataxia type 20. 1589 61

Spinocerebellar ataxia 25 (SCA25) is a rare form of autosomal dominant cerebellar ataxia associated with a severe sensory neuropathy. Clinical variability ranges from incomplete penetrance at age 61 to a Friedreich ataxia-like syndrome. The responsible locus was mapped to chromosome 2p in a large region of 14 Mbases in a single French kindred.
Cerebellum 2005
PMID:Spinocerebellar ataxia with sensory neuropathy (SCA25). 1589 62

Spinocerebellar ataxia type 1 (SCA1) is a late onset neurodegenerative disease characterized by cerebellar ataxia with variable degrees of ophthalmoplegia, pyramidal and extrapyramidal signs, and peripheral neuropathy. SCA1 is caused by the toxic effects triggered by an expanded polyglutamine (polyQ) within the protein ataxin 1 (Atxn1) resulting in variable degrees of neurodegeneration in the cerebellum, brainstem, and spinocerebellar tracts. The toxic gain-of-function mechanisms by which the polyQ expansion induces neuronal cell death are not fully understood and no effective therapies are yet available. Alterations in transcriptional regulation, calcium homeostasis, glutamate signaling/excitotoxicity, and impaired protein degradation are few recurrent events in the pathogenesis in SCA1. However, elucidating the molecular routes regulated by ataxin 1 is leading to the discovery of new pathways that are implicated in SCA1. This suggests that dominant-negative effects exerted by the mutant protein, rather than just gain-of-function mechanisms, might be also implicated in SCA1 pathogenesis. The challenge now is to determine how these responses account for the clinical manifestation of the disease symptoms and, ultimately, how this knowledge can be translated into the development of therapeutic strategies. Herein, we review the phenotype and most recent advances in our understanding of the physiopathological mechanisms of neurodegeneration in SCA1.
Cerebellum 2008
PMID:Clinical, genetic, molecular, and pathophysiological insights into spinocerebellar ataxia type 1. 1841 61

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited, neurodegenerative disease. It can manifest either with a cerebellar syndrome or as Parkinson's syndrome, while later stages involve mainly brainstem, spinal cord and thalamus. This particular atrophy pattern resembles sporadic multi-system-atrophy (MSA) and results in some clinical features indicative of SCA2, such as early saccade slowing, early hyporeflexia, severe tremor of postural or action type, and early myoclonus. For treatment, levodopa is temporarily useful for rigidity/bradykinesia and for tremor, magnesium for muscle cramps, but neuroprotective therapy will depend on the elucidation of pathogenesis. The disease cause lies in the polyglutamine domain of the protein ataxin-2, which can expand in families over successive generations resulting in earlier onset age and faster progression. Genetic testing in SCA2 and other polyglutamine disorders like the well-studied Huntington's disease is now readily available for family planning. Although these disorders differ clinically and in the affected neuron populations, it is not understood how the different polyglutamine proteins mediate such tissue specificity. The neuronal intranuclear inclusion bodies described in other polyglutamine disorders are not frequent in SCA2. For the quite ubiquitously expressed ataxin-2, a subcellular localization at the Golgi, the endoplasmic reticulum and the plasma membrane, in interaction with proteins of mRNA translation and of endocytosis have been observed. As a first victim of SCA2 degeneration, cerebellar Purkinje neurons may be preferentially susceptible to alterations of these subcellular pathways, and therefore our review aims to portray the particular profile of the SCA2 disease process and correlate it to the specific features of ataxin-2.
Cerebellum 2008
PMID:Spinocerebellar ataxia 2 (SCA2). 1841 84

Spinocerebellar ataxia 17 (SCA17) or Huntington's disease-like-4 is a neurodegenerative disease caused by the expansion above 44 units of a CAG/CAA repeat in the coding region of the TATA box binding protein (TBP) gene leading to an abnormal expansion of a polyglutamine stretch in the corresponding protein. Alleles with 43 and 44 repeats have been identified in sporadic cases and their pathogenicity remains uncertain. Furthermore, incomplete penetrance of pathological alleles with up to 49 repeats has been suggested. The imperfect nature of the repeat makes intergenerational instability extremely rare and de novo mutations are most likely the result of partial duplications. This is one of the rarer forms of autosomal dominant cerebellar ataxia but the associated phenotype is often severe, involving various systems (cerebral cortex, striatum, and cerebellum), with extremely variable age at onset (range: 3-75 years) and clinical presentation. This gene is thought to account for a small proportion of patients with a Huntington's disease-like phenotype and cerebellar signs. Parkinson's disease-like, Creutzfeldt-Jakob disease-like and Alzheimer disease-like phenotypes have also been described with small SCA17 expansions. The abnormal protein is expressed at the same level as its normal counterpart and forms neuronal intranuclear inclusions containing other proteins involved in protein folding or degradation. The increase in the size of the glutamine stretch enhances transcription in vitro, probably leading to transcription deregulation. Interestingly, the TBP protein mutated in SCA17 is recruited in the inclusions of other polyglutaminopathies, suggesting its involvement in the transcription down-regulation observed in these diseases.
Cerebellum 2008
PMID:Spinocerebellar ataxia 17 (SCA17) and Huntington's disease-like 4 (HDL4). 1841 87

Spinocerebellar ataxia 21 is a slowly progressive and mild ataxia associated with extrapyramidal signs. Affected subjects exhibit a moderate gait and limb ataxia variably associated with akinesia, tremor, rigidity, hyporeflexia, and mild cognitive impairment. The responsible gene has been assigned to a 19 Mbases interval on chromosome 7p in a single French family. No evidence of significant linkage to this locus was found in 21 other families obtained from the EUROSCA consortium. The locus interval contains several candidate genes that could be responsible for the disease. Direct sequencing of NDUFA4, PHF14, KIAA0960, ARLA4, ETV1, DGKB, HDAC9, FERD3L, ITGB8, and SP4 genes were performed, but all the direct mutation analyses were negative excluding pathogenic mutations associated with the disease. Therefore, the gene responsible for SCA21 remains to be identified.
Cerebellum 2008
PMID:Slowly progressive spinocerebellar ataxia with extrapyramidal signs and mild cognitive impairment (SCA21). 1841 88


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