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 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

Postmitotic neurons are resistant to gene delivery. However, lentiviral vectors allow the introduction of a foreign gene efficiently into neurons without significant toxicity to the infected cells (Sawada et al., Cerebellum 9(3):291-302, 2010). In addition, these vectors show a high tropism for neurons, and the transgenes they carry have been shown to be continuously expressed for at least a couple of years (Hirai, Cerebellum 7(3):273-8, 2008). We developed a method to express a foreign gene efficiently in cerebellar Purkinje cells in vivo (Takayama et al., Neurosci Lett 443(1):7-11, 2008; Torashima et al., Brain Res 1082(1):11-22, 2006, The Eur J Neurosci 24(2):371-80, 2006). Using our method, various experiments were carried out to study the pathophysiology of the cerebellum, including the investigation of a cerebellum-specific gene of unknown function, the generation and analysis of a mouse model of the spinocerebellar ataxia, and the rescue of an ataxic phenotype in mutant mice by introducing a defective gene or a therapeutic gene into the Purkinje cells. Here, we introduce our recent studies on expressing transgenes in the cerebellum using lentiviral vectors.
Cerebellum 2012 Jun
PMID:Basic research on cerebellar gene therapy using lentiviral vectors. 2212 Aug 47