Review
The Ins and Outs of a Polyglutamine Neurodegenerative Disease: Spinocerebellar Ataxia Type 1 (SCA1)

https://doi.org/10.1006/nbdi.2000.0305Get rights and content

Abstract

Polyglutamine neurodegenerative disorders are characterized by the expansion of a glutamine tract within the mutant disease-causing protein. Expression of the mutant protein induces a progressive loss of neuronal function and the subsequent neurodegeneration of a set of neurons characteristic to each disease. Spinocerebellar ataxia type 1 (SCA1) is one polyglutamine disease where various experimental model systems, in particular transgenic mice, have been utilized to dissect the molecular and cellular events important for disease. This review summarizes these findings and places them in a context of potential future research directions.

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  • Cited by (18)

    • 5′UTR-mediated regulation of Ataxin-1 expression

      2020, Neurobiology of Disease
      Citation Excerpt :

      Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative disease caused by the abnormal expansion of a CAG codon repeat in the open reading frame of the ATXN1 gene (Orr et al., 1993). Individuals with SCA1 display a progressive deterioration of balance and gait control, as well as swallowing and breathing difficulties, leading to premature death (Ashizawa et al., 2013; Orr, 2000; Orr et al., 1993; Zoghbi and Orr, 2009). Although the Ataxin-1 protein is expressed throughout the brain, and other parts of the body, a preferential loss of cerebellar Purkinje cells and a thinning of the brainstem are the main pathological findings in SCA1 (Seidel et al., 2012; Servadio et al., 1995).

    • Impairment of spinal motor neurons in spinocerebellar ataxia type 1-knock-in mice

      2013, Neuroscience Letters
      Citation Excerpt :

      However, disease alleles are pure CAG tracts ranging from 39 to 82 units [4]. SCA1 typically presents in the 4th decade (age range is 4–74 years) [18,23]. The patients show dysarthria, handwriting difficulties and limb ataxia as common symptoms [18,23].

    • Spinocerebellar ataxia type 2

      2012, Handbook of Clinical Neurology
      Citation Excerpt :

      Furthermore, in individuals with very large CAG expansions or in severe late stages of SCA2, an overlap with other polyglutamine diseases becomes apparent, since retinitis pigmentosa may be considered an overlap with SCA7, and myoclonus and epilepsy may be considered an overlap with DRPLA. In the clinical differential diagnosis of SCA2 in comparison with other SCAs, SCA1 may present with more pyramidal signs, executive dysfunction, hypermetric saccades, nystagmus, optic atrophy, dysphagia, and breathing problems (Bürk et al., 1996; Abele et al., 1997; Orr, 2000); SCA3 with more diplopia, hypometric saccades, motor neuron disease, neuropathy, extrapyramidal signs, spasticity, and impaired temperature discrimination (Schöls et al., 1997); SCA6 with a more restricted cerebellar picture and usually late onset beyond 50 years (Schöls et al., 1997, 1998); SCA7 with macular degeneration from retinitis pigmentosa and hyperreflexia (Michalik et al., 2004; Maschke et al., 2005), SCA10 with seizures and an increased occurrence among Mexicans; SCA12 with head action tremor upon manifestation; SCA13 with psychomotor retardation and early onset below 10 years of age; SCA14 with axial myoclonus in early-onset patients; SCA16 with rotary head tremor; SCA17 with psychiatric symptoms, chorea, dementia, and seizures; SCA18 with onset below 20 years of age; and SCA20 with dysphonia and palatal or lip tremor, Parkinson's disease with hyposmia and the absence of ataxia and saccade impairment (Manto, 2005; van de Warrenburg et al., 2005a). However, in view of the heterogeneity of heredoataxias, the many undefined variants and the clinical overlap, the diagnosis of SCA2 should always be based on molecular genetics.

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    Address correspondence to author at Institute of Human Genetics, University of Minnesota, Box 206, Minneapolis, MN 55455. Fax: (612) 626-2600. E-mail: [email protected].

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