Discovery of Therapeutics Targeting Oxidative Stress in Autosomal Recessive Cerebellar Ataxia: A Systematic Review

Autosomal recessive cerebellar ataxias (ARCAs) are a heterogeneous group of rare neurodegenerative inherited disorders. The resulting motor incoordination and progressive functional disabilities lead to reduced lifespan. There is currently no cure for ARCAs, likely attributed to the lack of understanding of the multifaceted roles of antioxidant defense and the underlying mechanisms. This systematic review aims to evaluate the extant literature on the current developments of therapeutic strategies that target oxidative stress for the management of ARCAs. We searched PubMed, Web of Science, and Science Direct Scopus for relevant peer-reviewed articles published from 1 January 2016 onwards. A total of 28 preclinical studies fulfilled the eligibility criteria for inclusion in this systematic review. We first evaluated the altered cellular processes, abnormal signaling cascades, and disrupted protein quality control underlying the pathogenesis of ARCA. We then examined the current potential therapeutic strategies for ARCAs, including aromatic, organic and pharmacological compounds, gene therapy, natural products, and nanotechnology, as well as their associated antioxidant pathways and modes of action. We then discussed their potential as antioxidant therapeutics for ARCAs, with the long-term view toward their possible translation to clinical practice. In conclusion, our current understanding is that these antioxidant therapies show promise in improving or halting the progression of ARCAs. Tailoring the therapies to specific disease stages could greatly facilitate the management of ARCAs

Discovery of Therapeutics Targeting Oxidative Stress in Autosomal Recessive Cerebellar Ataxia: A Systematic Review

Autosomal recessive cerebellar ataxias (ARCAs) are a heterogeneous group of rare neurodegenerative inherited disorders. The resulting motor incoordination and progressive functional disabilities lead to reduced lifespan. There is currently no cure for ARCAs, likely attributed to the lack of understanding of the multifaceted roles of antioxidant defense and the underlying mechanisms. This systematic review aims to evaluate the extant literature on the current developments of therapeutic strategies that target oxidative stress for the management of ARCAs. We searched PubMed, Web of Science, and Science Direct Scopus for relevant peer-reviewed articles published from 1 January 2016 onwards. A total of 28 preclinical studies fulfilled the eligibility criteria for inclusion in this systematic review. We first evaluated the altered cellular processes, abnormal signaling cascades, and disrupted protein quality control underlying the pathogenesis of ARCA. We then examined the current potential therapeutic strategies for ARCAs, including aromatic, organic and pharmacological compounds, gene therapy, natural products, and nanotechnology, as well as their associated antioxidant pathways and modes of action. We then discussed their potential as antioxidant therapeutics for ARCAs, with the long-term view toward their possible translation to clinical practice. In conclusion, our current understanding is that these antioxidant therapies show promise in improving or halting the progression of ARCAs. Tailoring the therapies to specific disease stages could greatly facilitate the management of ARCAs

Exploratory and Confirmatory Factor Analyses of the Short Grit Scale (Grit-S) for Malaysian Undergraduate Students

The 8-item Short Grit Scale (Grit-S; Duckworth & Quinn, 2009) is a measure of the two aspects of grit: consistency of interests and perseverance of effort. While the majority of the past studies supported the two-factor model, some found cultural differences. Two studies were carried out to test the factor structure of the Grit-S in a sample of Malaysian undergraduate students (total N = 1109). Exploratory factor analysis (Study 1) revealed two factors. Item 2 for perseverance subscale was removed due to unsatisfactory factor loading. Further analysis of the seven items supported the two-factor model. Confirmatory factor analyses (Study 2) supported the superiority of the two correlated-factor model with 7 items. Moreover, the consistency and perseverance scores showed acceptable internal consistency. The current research contributes to the literature by lending further support to the theoretical two-factor structure of the Grit-S and revealing potential cultural differences in the items. Future studies are thus recommended to address these cultural differences and confirm the usability of the 7-item Grit-S in the Malaysian context