The pathogenesis of spinocerebellar ataxia

@article{Koeppen2008ThePO,
  title={The pathogenesis of spinocerebellar ataxia},
  author={Arnulf H. Koeppen},
  journal={The Cerebellum},
  year={2008},
  volume={4},
  pages={62-73}
}
  • A. Koeppen
  • Published 2008
  • Biology, Medicine
  • The Cerebellum
Six forms of spinocerebellar ataxia (SCA) are caused by pathological cytosine-adenine-guanine (CAG) trinucleotide repeat expansions in the coding region of the mutated genes. The translated proteins contain abnormally long polyglutamine stretches, and SCA-1, SCA-2, SCA-3/Machado-Joseph disease (MJD), SCA-6, SCA-7, and SCA-17 are “polyglutamine diseases”. Despite their clinical and genetic heterogeneity, the ataxia-causing lesions in the brain invariably affect the “cerebellar module” that is… 
Spinocerebellar ataxia type 1.
TLDR
The most common presentation of SCA1 is dominant ataxia 'plus', characterized by cerebellar dysfunctions variably associated with slow saccades, ophthalmoplegia, pyramidal and extrapyramidal features, mild to moderate dementia, amyotrophy, and peripheral neuropathy.
Spinocerebellar ataxia type 6.
TLDR
This chapter will discuss as well the molecular mechanisms possibly associated with SCA6 pathology and their implication for the development of future treatment.
Brain pathology of spinocerebellar ataxias
TLDR
The genetic and clinical background of the known SCAs are reported, the state of neuropathological investigations of brain tissue from SCA patients in the final disease stages are presented, and detailed molecular and pathogenetic consequences remain to be determined.
The clinical diagnosis of autosomal dominant spinocerebellar ataxias
TLDR
In all ataxia patients with proven or suspected autosomal dominant mode of inheritance, the available molecular genetic tests for SCA mutations should be performed, depending on the geographical origin of the family, these tests will lead to positive diagnostic results in at least half of the families.
Spinocerebellar [corrected] Ataxia Type 6: Molecular Mechanisms and Calcium Channel Genetics.
TLDR
The IRES, as the translational control element of α1ACT, provides a potential therapeutic target for the treatment of SCA6, and understanding the function ofα1ACT in physiological and pathological conditions may elucidate the pathogenesis ofSCA6.
Spinocerebellar Ataxia Type 3: A Case Report and Literature Review.
TLDR
The clinical and neuropathologic features in a case of SCA3 with unique findings are described, including involvement of the inferior olivary nucleus and cerebellar Purkinje cell layer, which are classically spared in the disease.
Pathogenic mechanisms underlying spinocerebellar ataxia type 1
TLDR
The current understanding of the molecular pathogenesis of the SCAs is detailed, focusing primarily on the first described autosomal dominant spinocerebellar ataxia, SCA1, as well as the emerging common core mechanisms across the various SCAs.
Pathoanatomy of Cerebellar Degeneration in Spinocerebellar Ataxia Type 2 (SCA2) and Type 3 (SCA3)
TLDR
It is demonstrated that the Cerebellar Purkinje cell layer and all four deep cerebellar nuclei consistently undergo considerable neuronal loss in SCA2 and SCA3.
Chapter 4 Clinical and Genetic Aspects of Spinocerebellar Ataxias with Emphasis on Polyglutamine Expansions
TLDR
This chapter discusses the clinical and genetical aspects of spinocerebellar ataxias with emphasis on polyglutamine expansions, and genetic diagnosis, now possible in several of these disorders, allows accurate genetic counseling and offers the possibility of presymptomatic and prenatal testing.
Machado-Joseph Disease: from first descriptions to new perspectives
Machado-Joseph Disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), represents the most common form of SCA worldwide. MJD is an autosomal dominant neurodegenerative disorder of late
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 44 REFERENCES
Clinical features and neuropathology of autosomal dominant spinocerebellar ataxia (SCA17)
TLDR
It is concluded that SCA17 is rare among white SCA patients and should be considered in sporadic and familial cases of ataxia with accompanying psychiatric symptoms and dementia.
Neuronal intranuclear inclusions in SCA2: a genetic, morphological and immunohistochemical study of two cases.
TLDR
The results support the view that intranuclear inclusions are an integral part of the pathology of this mutation, and present the cases of a 41-year-old man and a 54- year-old woman who died after a long illness characterized by severe cerebellar ataxia.
Synapses in the hereditary ataxias.
TLDR
Assessment of synapses in the hereditary ataxias by the immunocytochemical and immunofluorescent visualization of SNAP-25 correlated more precisely with the severity of the ataxia than the changes in the cerebellar cortex.
Polyglutamine expansion as a pathological epitope in Huntington's disease and four dominant cerebellar ataxias
TLDR
The characterization of a monoclonal antibody is reported that selectively recognizes polyglutamine expansion in the proteins implicated in HD and in spinocerebellar ataxia (SCA) 1 and 3 and detects specific pathological proteins expected to contain such expansion.
Cell death in polyglutamine diseases
TLDR
This review summarizes the clinical and genetic features of each CAG repeat disorder and focuses on the common mechanistic steps involved in the disease progression of these so-called polyglutamine diseases.
SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein.
TLDR
A novel spinocerebellar ataxia (SCA) form in four Japanese pedigrees is identified which is caused by an abnormal CAG expansion in the TATA-binding protein (TBP) gene, a general transcription initiation factor, and it has been added to the group of polyglutamine diseases.
A new dominant spinocerebellar ataxia linked to chromosome 19q13.4-qter.
TLDR
A 4-generation American family of English and Dutch ethnicity with a pure cerebellar ataxia displaying an autosomal dominant pattern of inheritance is identified and a gene for an autosomic dominant SCA to chromosome 19q13 is mapped in one family.
Expansion of a novel CAG trinucleotide repeat in the 5′ region of PPP2R2B is associated with SCA12
TLDR
A novel form of autosomal dominant SCA is identified in a large pedigree ('R') of German descent, termed SCA12, which resembles the spinocerebellar ataxias more closely than any other form of neurodegenerative disorder.
Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10
TLDR
Analysis of chromosomes from unaffected individuals of various ethnic origins showed a range of 10 to 22 ATTCT repeats with no evidence of expansions, indicating that the new SCA10 intronic ATTCT pentanucleotide repeat inSCA10 patients is unstable and represents the largest microsatellite expansion found so far in the human genome.
Cytoplasmic and nuclear polyglutamine aggregates in SCA6 Purkinje cells
TLDR
The authors show that small aggregates, labeled by a monoclonal antibody 1C2 that preferentially detects expanded polyglutamine larger than that in SCA6 mutation, are present mainly in the cytoplasm but also in the nucleus of Purkinje cells.
...
1
2
3
4
5
...