Homozygous Machado–Joseph disease presenting as REM sleep behaviour disorder and prominent psychiatric symptoms

Fukutake, Toshio; Shinotoh, Hitoshi; Nishino, Hiroshi; Ichikawa, Yaeko; Goto, Jun; Kanazawa, Ichiro; Hattori, Takaaki

doi:10.1046/j.1468-1331.2002.00335.x

Cited by 53 publications

(25 citation statements)

References 17 publications

(23 reference statements)

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“…Rare alleles of intermediate repeat length fall between the clearly normal and mutant ranges and are not associated with classical clinical features of disease (Gu et al , 2004; Maciel et al , 2001; Padiath et al , 2005; Paulson, 2007; Takiyama et al , 1997; van Alfen et al , 2001; van Schaik et al , 1997). Cases of homozygosity are extremely rare in MJD; the few described homozygous patients appear to show a more severe form of disease suggesting a gene dosage effect (Carvalho et al , 2008; Fukutake et al , 2002; Lang et al , 1994; Lerer et al , 1996; Sobue et al , 1996; Takiyama et al , 1995). …”

Section: The Disease Gene Atxn3mentioning

confidence: 99%

Toward understanding Machado–Joseph disease

Costa

Paulson

2012

Progress in Neurobiology

232

236

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Machado-Joseph disease (MJD), also known as Spinocerebellar ataxia type 3 (SCA3), is the most common inherited spinocerebellar ataxia and one of many polyglutamine neurodegenerative diseases. In MJD, a CAG repeat expansion encodes an abnormally long polyglutamine (polyQ) tract in the disease protein, ATXN3. Here we review MJD, focusing primarily on the function and dysfunction of ATXN3 and on advances toward potential therapies. ATXN3 is a deubiquitinating enzyme (DUB) whose highly specialized properties suggest that it participates in ubiquitin-dependent proteostasis. By virtue of its interactions with VCP, various ubiquitin ligases and other ubiquitin-linked proteins, ATXN3 may help regulate the stability or activity of many proteins in diverse cellular pathways implicated in proteotoxic stress response, aging, and cell differentiation. Expansion of the polyQ tract in ATXN3 is thought to promote an altered conformation in the protein, leading to changes in interactions with native partners and to the formation of insoluble aggregates. The development of a wide range of cellular and animal models of MJD has been crucial to the emerging understanding of ATXN3 dysfunction upon polyQ expansion. Despite many advances, however, the principal molecular mechanisms by which mutant ATXN3 elicits neurotoxicity remain elusive. In a chronic degenerative disease like MJD, it is conceivable that mutant ATXN3 triggers multiple, interconnected pathogenic cascades that precipitate cellular dysfunction and eventual cell death. A better understanding of these complex molecular mechanisms will be important as scientists and clinicians begin to focus on developing effective therapies for this incurable, fatal disorder.

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Section: The Disease Gene Atxn3mentioning

confidence: 99%

Toward understanding Machado–Joseph disease

Costa

Paulson

2012

Progress in Neurobiology

232

236

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“…Diverse etiologies include cases of tauopathy related parkinsonian syndromes (Progressive supranuclear palsy, Guadaloupean parkinsonism) [149][150][151], TDP43opathies (frontotemporal dementia, amyotrophic lateral sclerosis) [7,152], amyloidopathies (Alzheimer's disease) [7,153]. RBD has also been associated with some trinucleatide repeat disorders including spinal cerebellar ataxia type 3 (SCA3) [154][155][156][157] and Huntington's disease [158]. However, with the notable exception of SCA3, none of these conditions have prevalence rates similar to synuclein disorders.…”

Section: Non-synuclein Neurodegenerative Etiologiesmentioning

confidence: 99%

Parasomnias: An Updated Review

2012

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Parasomnias are abnormal behaviors emanating from or associated with sleep. Sleepwalking and related disorders result from an incomplete dissociation of wakefulness from nonrapid eye movement (NREM) sleep. Conditions that provoke repeated cortical arousals, or promote sleep inertia lead to NREM parasomnias by impairing normal arousal mechanisms. Changes in the cyclic alternating pattern, a biomarker of arousal instability in NREM sleep, are noted in sleepwalking disorders. Sleep-related eating disorder (SRED) is characterized by a disruption of the nocturnal fast with episodes of feeding after an arousal from sleep. SRED is often associated with the use of sedative-hypnotic medications; in particular, the widely prescribed benzodiazepine receptor agonists. Recently, compelling evidence suggests that nocturnal eating may in some cases be a nonmotor manifestation of Restless Legs Syndrome (RLS). rapid eye movement (REM) Sleep Behavior Disorder (RBD) is characterized by a loss of REM paralysis leading to potentially injurious dream enactment. The loss of atonia in RBD often predates the development of Parkinson's disease and other disorders of synuclein pathology. Parasomnia behaviors are related to an activation (in NREM parasomnias) or a disinhibition (in RBD) of central pattern generators (CPGs). Initial management should focus on decreasing the potential for sleep-related injury followed by treating comorbid sleep disorders. Clonazepam and melatonin appear to be effective therapies in RBD, whereas paroxetine has been reported effective in some cases of sleep terrors. At this point, pharmacotherapy for other parasomnias is less certain, and further investigations are necessary.Keywords Parasomnia . Sleepwalking . Sleep terrors . REM sleep behavior disorder . Restless legs syndrome Classification of ParasomniasParasomnias are typically classified by the sleep state from which they arise: non-rapid eye movement sleep (NREM) and rapid eye movement sleep (REM) (see Table 1 NREM parasomnias include: confusional arousals, sleepwalking disorder, and sleep terrors. These behaviors arise when the cortex incompletely arouses from deep NREM sleep, often due to comorbid conditions that provoke repeated arousal or promote sleep inertia. Changes in the cyclic alternating pattern, a biomarker of arousal instability in NREM sleep, are noted in sleepwalking and related disorders [3].Sleep-related eating disorder (SRED) is currently classified in the International Classification of Sleep Disorders, 2nd edition (ICSD-2) under "Other Parasomnia" [1]. However the vast majority of SRED cases emanate from NREM [4], and the complex amnestic behaviors with ambulation are striking similar to sleepwalking [5]. Furthermore, both SRED and sleepwalking are frequently triggered by sedating agents in the setting of underlying motor restlessness [6]. Thus, considering these similarities, SRED will be reviewed immediately after NREM parasomnias.REM sleep behavior disorder is the most clinically relevant REM parasomnia. The loss of atoni...

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“…Several clinical investigations showed that dementia in SCA3 might be less frequent (5–13%) than in other SCAs [10, 18, 31]. However, it has been reported that SCA3 patients do have various cognitive and psychiatric disorders, such as REM sleep behavior disorder [32] and delirium [33]. Maruff et al [34] examined cognitive function in 6 patients with genetically confirmed SCA3 using a series of subtests from the Cambridge Neuropsychological Test Automated Battery.…”

Section: Spinocerebellar Ataxia Type 3 (Machado-joseph Disease)mentioning

confidence: 99%

Cognitive Impairment in Spinocerebellar Degeneration

et al. 2009

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It has been reported that patients with spinocerebellar degenerations (SCDs) have cognitive dysfunction as well as limb and truncal ataxia, dysarthria and dysphagia. We review cognitive dysfunction in common types of SCD, including spinocerebellar ataxia types 1, 2, 3, 6, and 17, dentatorubral-pallidoluysian atrophy, Friedreich’s ataxia, and multiple system atrophy. There are few studies that address cognitive function in SCD. Although there are few comparison studies among the various SCDs, cognitive dysfunction may be more common and severe in spinocerebellar ataxia type 17 and dentatorubral-pallidoluysian atrophy. While cognitive dysfunction in SCD appears to represent frontal dysfunction, the mechanisms of cognitive dysfunction have not been directly clarified. Nevertheless, various lesions, including those in the cerebrocerebellar circuitry, cortico-striatal-thalamocortical circuitry, and the frontal lobe, may influence cognitive function to various degrees for each disease.

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Homozygous Machado–Joseph disease presenting as REM sleep behaviour disorder and prominent psychiatric symptoms

Cited by 53 publications

References 17 publications

Toward understanding Machado–Joseph disease

Toward understanding Machado–Joseph disease

Parasomnias: An Updated Review

Cognitive Impairment in Spinocerebellar Degeneration

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