Trehalose Attenuates the Gait Ataxia and Gliosis of Spinocerebellar Ataxia Type 17 Mice

Chen, Zhi Zhong; Wang, Chen; Lee, Guan Chiun; Hsu, Ho Chiang; Wu, Tzu Ling; Lin, Chia Wei; Kang, Chih Ming; Lee-Chen, Guey Jen; Huang, Hei Jen; Hsieh-Li, Hsiu Mei

doi:10.1007/s11064-015-1530-4

Cited by 38 publications

(24 citation statements)

References 34 publications

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“…These animals also displayed a reduction in striatum atrophy and in aggregate number. Similarly, treatment of SCA17 transgenic mice with 4% trehalose increased latency to fall in the rotarod and mediated amelioration of gait disturbances in the footprint analysis [37].…”

Section: Discussionmentioning

confidence: 88%

Trehalose alleviates the phenotype of Machado–Joseph disease mouse models

et al. 2020

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Background: Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3, is the most common of the dominantly inherited ataxias worldwide and is characterized by mutant ataxin-3 aggregation and neuronal degeneration. There is no treatment available to block or delay disease progression. In this work we investigated whether trehalose, a natural occurring disaccharide widely used in food and cosmetic industry, would rescue biochemical, behavioral and neuropathological features of an in vitro and of a severe MJD transgenic mouse model. Methods: Two MJD animal models, a lentiviral based and a transgenic model, were orally treated with 2% trehalose solution for a period of 4 and 30 weeks, respectively. Motor behavior (rotarod, grip strength and footprint patterns) was evaluated at different time points and neuropathological features were evaluated upon in-life phase termination. Results: Trehalose-treated MJD mice equilibrated for a longer time in the rotarod apparatus and exhibited an improvement of ataxic gait in footprint analysis. Trehalose-mediated improvements in motor behaviour were associated with a reduction of the MJD-associated neuropathology, as MJD transgenic mice treated with trehalose presented preservation of cerebellar layers thickness and a decrease in the size of ataxin-3 aggregates in Purkinje cells. In agreement, an improvement of neuropathological features was also observed in the full length lentiviral-based mouse model of MJD submitted to 2% trehalose treatment. Conclusions: The present study suggests trehalose as a safety pharmacological strategy to counteract MJD-associated behavioural and neuropathological impairments.

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Section: Discussionmentioning

confidence: 88%

Trehalose alleviates the phenotype of Machado–Joseph disease mouse models

et al. 2020

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“…Trehalose, thought to act as a chemical chaperone, is able to stabilize polyQ proteins in their native conformation; however, it is also known to be an autophagy inducer (discussed below) . This compound was shown to be efficient in HD cellular and animal models and recently in SCA17 mice . Geranylgeranylacetone, a molecule capable of enhancing the expression of Hsp70, Hsp90, and Hsp105 through induction of HSF‐1 activity, proved to inhibit nuclear accumulation of mutant AR, to ameliorate motor behavior and increase survival in a SBMA mouse model .…”

Section: Therapeutic Strategies For Polyq Diseasesmentioning

confidence: 99%

Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Efforts

Duarte‐Silva

Maciel

2016

Medicinal Research Reviews

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Polyglutamine (PolyQ) diseases are a group of neurodegenerative disorders caused by the expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats in the coding region of specific genes. This leads to the production of pathogenic proteins containing critically expanded tracts of glutamines. Although polyQ diseases are individually rare, the fact that these nine diseases are irreversibly progressive over 10 to 30 years, severely impairing and ultimately fatal, usually implicating the full-time patient support by a caregiver for long time periods, makes their economic and social impact quite significant. This has led several researchers worldwide to investigate the pathogenic mechanism(s) and therapeutic strategies for polyQ diseases. Although research in the field has grown notably in the last decades, we are still far from having an effective treatment to offer patients, and the decision of which compounds should be translated to the clinics may be very challenging. In this review, we provide a comprehensive and critical overview of the most recent drug discovery efforts in the field of polyQ diseases, including the most relevant findings emerging from two different types of approaches-hypothesis-based candidate molecule testing and hypothesis-free unbiased drug screenings. We hereby summarize and reflect on the preclinical studies as well as all the clinical trials performed to date, aiming to provide a useful framework for increasingly successful future drug discovery and development efforts.

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“…For gait analysis, CatWalk 10.6 (Noldus Information Technology) was used. Mice walked freely across the glass platform for three or more consecutive steps without stopping and from these runs; average values were obtained for analysis.…”

Section: Methodsmentioning

confidence: 99%

Effect of trehalose on manganese‐induced mitochondrial dysfunction and neuronal cell damage in mice

Liu

Jing

Liu

et al. 2019

Basic Clin Pharma Tox

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Chronic overexposure to manganese (Mn) has been verified to induce mitochondrial dysfunction, which is related to oxidative damage. The autophagic‐lysosomal degradation pathway plays a vital role in the removal of impaired mitochondria through a specific quality control mechanism termed mitophagy. However, trehalose functions as an inducer of autophagy by an mTOR‐independent mechanism, and little data report its effect on Mn‐induced mitochondrial dysfunction. To explore the possibility that trehalose could be effective in interfering with the Mn‐induced mitochondrial dysfunction, we used trehalose (2% and 4% (g/vol (mL))) in a mouse model of manganism. Our data showed that mice developed weary motor and behavioural deficits after exposure to Mn for 6 weeks. Overexposure to Mn resulted in mitochondrial dysfunction and neuronal cell damage in the basal nuclei of mice, which could be ameliorated by trehalose pre‐treatment. Moreover, our results indicated that trehalose pre‐treatment significantly reduced the oxidative damage and enhanced the activation of mitophagy. The findings clearly demonstrated that trehalose could relieve Mn‐induced mitochondrial and neuronal cell damage through its antioxidative and mitophagy‐inducing effects.

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Trehalose Attenuates the Gait Ataxia and Gliosis of Spinocerebellar Ataxia Type 17 Mice

Cited by 38 publications

References 34 publications

Trehalose alleviates the phenotype of Machado–Joseph disease mouse models

Trehalose alleviates the phenotype of Machado–Joseph disease mouse models

Discovery of Therapeutic Approaches for Polyglutamine Diseases: A Summary of Recent Efforts

Effect of trehalose on manganese‐induced mitochondrial dysfunction and neuronal cell damage in mice

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