Inhibition of acetylcholinesterase (AChE) is a common used treatment option for Alzheimer's disease. However, there has been limited research on the potential use of AChE inhibitors for the treatment of Machado-Joseph disease (MJD)/Spinocerebellar Ataxia 3 (SCA3), in spite of the positive results using AChE inhibitors in patients with other inherited ataxias. MJD/SCA3, the most common form of dominant Spinocerebellar Ataxia worldwide, is caused by an expansion of the polyglutamine tract within the ataxin-3 protein, and is characterized by motor impairments. Our study shows that administration of the AChE inhibitor neostigmine is beneficial in treating the locomotion defective phenotype of a SCA3/MJD model of C. elegans and highlights the potential contribution of AChE enzymes to mutant ataxin-3-mediated toxicity.
Copyright: © 2024 by the authors.
Financial support was provided by the Moulton-Barrett Research Scholarship from Tenovus Scotland (Charity Number SC009675) (PhD studentship to F.P.) and the Erasmus+ program (to F.P.). At University of Minho, this work has been developed under the scope of the projects NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been also funded by FEDER through the Competitiveness Factors Operational Programme (COMPETE) or through the Competitiveness Internationalization Operational Programme (POCI), by National funds through the Foundation for Science and Technology (FCT) under the scope of the project UID/Multi/50026/2019 and POCI-01-0145-FEDER-0 31987 (to A.T.-C.) respectively.