Mitochondrial impairments contribute to Spinocerebellar ataxia type 1 progression and can be ameliorated by the mitochondria-targeted antioxidant MitoQ

Abstract

Mitochondrial impairments contribute to Spinocerebellar ataxia type 1 progression and can be ameliorated by the mitochondria-targeted antioxidant MitoQ, Free Radical Biology and Medicine, http://dx.doi.org/10.1016/j.freeradbiomed.2016.07.005 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Oxidative Stress in Neurodegenerative Diseases: From Molecular Mechanisms to Clinical Applications

“…Mutant ATXN1 can affect the stability of RAR-related orphan receptor alpha (ROR α ), which plays an important role in Purkinje cell functions. Decreased gene expression of RORα has been associated with ataxia and cerebellar hypoplasia [134, 135]. …”

“…While most types of SCAs are suggested as genetic diseases correlated with ATXN mutation, other pathogenic mechanisms that involve the dysfunction of mitochondria have been proposed [134, 135]. Hakonen et al observed respiratory complex I deficiency and mitochondrial DNA depletion in the brain of infantile-onset SCA individuals [136].…”

“…A study conducted by Stucki et al found elevated OS and significant mitochondrial alterations in the Purkinje cells of SCA1. They suspect that there is a potential correlation between the progression of SCA and mitochondrial impairments caused by OS (Figure 1()) [135]. Correspondingly, the study examined the effects of MitoQ (a mitochondrial antioxidant) using a SCA mouse model.…”

“…Correspondingly, the study examined the effects of MitoQ (a mitochondrial antioxidant) using a SCA mouse model. It was found that long-term administration of MitoQ significantly restores mitochondrial morphology and functions in Purkinje cells as well as alleviates SCA1-related symptoms such as motor incoordination [135]. Their findings show the potential of using mitochondria-targeted antioxidants as a treatment for SCA1.…”

Purkinje cell COX deficiency and mtDNA depletion in an animal model of spinocerebellar ataxia type 1

“…Similarly, the other SCA1 mouse model, SCA1 154Q/2Q (Watase et al, ) and the transgenic mice for AFG3L2, the gene responsible for autosomal dominant SCA28 (Di Bella et al, ), display cerebellar mitochondrial dysfunction at histochemical and molecular level (Maltecca et al, ; Stucki et al, ).…”