Reactive nitrogen species as therapeutic targets for autophagy/mitophagy modulation to relieve neurodegeneration in multiple sclerosis: potential application for drug discovery

Abstract

<p><a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/multiple-sclerosis" title="Learn more about Multiple sclerosis from ScienceDirect's AI-generated Topic Pages">Multiple sclerosis</a> (MS) is a neuroinflammatory disease with limited therapeutic effects, eventually developing into handicap. Seeking novel therapeutic strategies for MS is timely important. Active autophagy/mitophagy could mediate <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/neurodegeneration" title="Learn more about neurodegeneration from ScienceDirect's AI-generated Topic Pages">neurodegeneration</a>, while its roles in MS remain controversial. To elucidate the exact roles of autophagy/mitophagy and reveal its in-depth regulatory mechanisms, we conduct a systematic literature study and analyze the factors that might be responsible for divergent results obtained. The dynamic change levels of autophagy/mitophagy appear to be a determining factor for final neuron fate during MS pathology. Excessive neuronal autophagy/mitophagy contributes to <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/neurodegeneration" title="Learn more about neurodegeneration from ScienceDirect's AI-generated Topic Pages">neurodegeneration</a> after disease onset at the active MS phase. <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/reactive-nitrogen-species" title="Learn more about Reactive nitrogen species from ScienceDirect's AI-generated Topic Pages">Reactive nitrogen species</a> (RNS) serve as key regulators for redox-related modifications and participate in autophagy/mitophagy modulation in MS. <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/nitric-oxide" title="Learn more about Nitric oxide from ScienceDirect's AI-generated Topic Pages">Nitric oxide</a> (^•NO) and <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/peroxynitrite" title="Learn more about peroxynitrite from ScienceDirect's AI-generated Topic Pages">peroxynitrite</a> (ONOO⁻), two representative RNS, could nitrate or nitrosate Drp1/parkin/PINK1 pathway, activating excessive mitophagy and aggravating neuronal injury. Targeting RNS-mediated excessive autophagy/mitophagy could be a promising strategy for developing novel anti-MS <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/chemotherapeutic-agent" title="Learn more about drugs from ScienceDirect's AI-generated Topic Pages">drugs</a>. In this review, we highlight the important roles of RNS-mediated autophagy/mitophagy in neuronal injury and review the potential therapeutic compounds with the bioactivities of inhibiting RNS-mediated autophagy/mitophagy activation and attenuating MS progression. Overall, we conclude that reactive nitrogen species could be promising therapeutic targets to regulate autophagy/mitophagy for multiple sclerosis <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/therapeutic-procedure" title="Learn more about treatment from ScienceDirect's AI-generated Topic Pages">treatment</a>.</p>