Abstract
Neurodegenerative polyglutamine (polyQ) disorders are caused by trinucleotide repeat expansions within the coding region of disease-causing genes. PolyQ-expanded proteins undergo conformational changes leading to the formation of protein inclusions which are associated with selective neuronal degeneration. Several lines of evidence indicate that these mutant proteins are associated with oxidative stress, proteasome impairment and microglia activation. These events may correlate with the induction of inflammation in the nervous system and disease progression. Here, we review the effect of polyQ-induced oxidative stress in cellular and animal models of polyQ diseases. Furthermore, we discuss the interplay between oxidative stress, neurodegeneration and neuroinflammation using as an example the well-known neuroinflammatory disease, Multiple Sclerosis. Finally, we review some of the pharmaceutical interventions which may delay the onset and progression of polyQ disorders by targeting disease-associated mechanisms.
Highlights
NDDs are associated with mutations in proteins which seem to be interconnected at the molecular level; for example, recent reports indicate that α-synuclein or ataxin-1 (ATXN1), proteins related to PD and spinocerebellar ataxia type-1 (SCA1), respectively, may represent risk factors for the pathogenesis and progression of AD or Multiple Sclerosis (MS) [2,3]
We present evidence on the induction of neuroinflammation in animal models and discuss the interplay between neurodegeneration and neuroinflammation using as an example the well-known neuroinflammatory disease Multiple Sclerosis (MS)
Regardless of the factors contributing to the buildup of oxidative burden, it was reRegardless of the factors contributing to the buildup of oxidative burden, it was peatedly shown that antioxidants attenuate several of the phenotypes manifested in repeatedly shown that antioxidants attenuate several of the phenotypes manifested in polyQ animal models
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. NDDs are associated with mutations in proteins which seem to be interconnected at the molecular level; for example, recent reports indicate that α-synuclein or ataxin-1 (ATXN1), proteins related to PD and spinocerebellar ataxia type-1 (SCA1), respectively, may represent risk factors for the pathogenesis and progression of AD or Multiple Sclerosis (MS) [2,3] Revealing such interconnections may facilitate the delineation of the pathogenic mechanisms and the development of novel therapeutic approaches in NDDs. Polyglutamine diseases (polyQ) are a group of rare, inherited and fatal NDDs caused by the expansion of trinucleotide repeats (CAG) encoding for glutamine within the coding region of various unrelated genes. We describe compounds with a potential therapeutic value which are currently tested in preclinical or clinical studies
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
