Mouse Models of Spinocerebellar Ataxia Type 3 (Machado-Joseph Disease)

Gould, Veronica F. Colomer

doi:10.1007/s13311-012-0117-x

Cited by 31 publications

(11 citation statements)

References 52 publications

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“…TgPED mice also show foot clasping, a symptom reported in several other transgenic mice bearing different neurological alterations such as mice deficient for Phospholipase A2 25 , Nuclear factor IA 26 , CREB 27 , Junctophilin 28 , HD gene gene with consequent striatal dysfunction 29 , SCA3 mice 30 , pPS1-A246E mutation 31 , Caveolin 32 , Npas3 33 , mGAT1 34 and mice over expressing BMP4 35 . Due to largely different behavioral phenotype of these animals, foot clasping should be considered as a rather aspecific neurological symptom.…”

Section: Discussionmentioning

confidence: 73%

Parkinson-like phenotype in insulin-resistant PED/PEA-15 transgenic mice

Perruolo

Viggiano

Fiory

et al. 2016

Sci Rep

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Neurological abnormalities, such as Parkinson-like disorders (PlD), are often co-morbidities of Type 2 Diabetic (T2D) patients, although the epidemiological link between these two disorders remains controversial. The PED/PEA-15 protein represents a possible candidate linking T2D and PD, because it is increased in subjects with T2D and is highly expressed in the brain. To test this hypothesis, we have analyzed the neurological and neurochemical phenotype of transgenic mice overexpressing PED/PEA-15 (tgPED). These mice develop impaired glucose tolerance and insulin resistance, accompanied by neurological features resembling PlD: feet clasping, slow and delayed locomotor movements in different behavioral tests in absence of clear cognitive deficits, ataxia or anxiety. Morphological analysis of the brains showed selective modifications of metabolic activity in the striatal region. In the same region, we have observed 26% decrease of dopamine fibers, confirmed by immunohistochemistry and Western Blot for tyrosine hydroxylase. Moreover, they also showed 48% reduction of dopamine levels in the striatum. Thus the tgPED mice may represent a genetic animal model of neurological disease linked to T2D.

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Section: Discussionmentioning

confidence: 73%

Parkinson-like phenotype in insulin-resistant PED/PEA-15 transgenic mice

Perruolo

Viggiano

Fiory

et al. 2016

Sci Rep

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“…Thus, a combination of computational models and mouse models is clinically informative for human SCAs. Several SCA mouse models have been developed (Burright et al, 1995 ; Huynh et al, 2000 ; van de Leemput et al, 2007 ; Colomer Gould, 2012 ; Kelp et al, 2013 ). As virtual model neurons are created, details of the computational models are validated by comparison with experimental data in these mice (Xu et al, 2003 ; Marasco et al, 2012 ), with an end to translation to humans (Figure 1 ).…”

Section: Clinical Translationmentioning

confidence: 99%

Computational neurobiology is a useful tool in translational neurology: the example of ataxia

2015

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Hereditary ataxia, or motor incoordination, affects approximately 150,000 Americans and hundreds of thousands of individuals worldwide with onset from as early as mid-childhood. Affected individuals exhibit dysarthria, dysmetria, action tremor, and diadochokinesia. In this review, we consider an array of computational studies derived from experimental observations relevant to human neuropathology. A survey of related studies illustrates the impact of integrating clinical evidence with data from mouse models and computational simulations. Results from these studies may help explain findings in mice, and after extensive laboratory study, may ultimately be translated to ataxic individuals. This inquiry lays a foundation for using computation to understand neurobiochemical and electrophysiological pathophysiology of spinocerebellar ataxias and may contribute to development of therapeutics. The interdisciplinary analysis suggests that computational neurobiology can be an important tool for translational neurology.

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“…More than 10 transgenic models for SCA3 have been published, all with variable differences in pathology and phenotype and most of them showing a mild form of neurodegeneration (Gould, 2012). A summary of the most commonly used mouse models and their key characteristics is shown in Table 2.…”

Section: Animal Models For Sca3mentioning

confidence: 99%

Gene Therapy for Neurodegenerative Diseases: Slowing Down the Ticking Clock

Martier

Konstantinova

2020

Front. Neurosci.

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Gene therapy is an emerging and powerful therapeutic tool to deliver functional genetic material to cells in order to correct a defective gene. During the past decades, several studies have demonstrated the potential of AAV-based gene therapies for the treatment of neurodegenerative diseases. While some clinical studies have failed to demonstrate therapeutic efficacy, the use of AAV as a delivery tool has demonstrated to be safe. Here, we discuss the past, current and future perspectives of gene therapies for neurodegenerative diseases. We also discuss the current advances on the newly emerging RNAi-based gene therapies which has been widely studied in preclinical model and recently also made it to the clinic.

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Mouse Models of Spinocerebellar Ataxia Type 3 (Machado-Joseph Disease)

Cited by 31 publications

References 52 publications

Parkinson-like phenotype in insulin-resistant PED/PEA-15 transgenic mice

Parkinson-like phenotype in insulin-resistant PED/PEA-15 transgenic mice

Computational neurobiology is a useful tool in translational neurology: the example of ataxia

Gene Therapy for Neurodegenerative Diseases: Slowing Down the Ticking Clock

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