Chloroquine, the Coronavirus Crisis, and Neurodegeneration: A Perspective

Abstract

On the verge of the ongoing coronavirus pandemic, in vitro data suggested that chloroquine, and its analog hydroxychloroquine, may be useful in controlling SARS-CoV-2 infection. Efforts are ongoing in order to test this hypothesis in clinical trials. Some studies demonstrated no evidence of efficacy, whereas in some cases results were retracted after reporting. Despite the lack of scientific validation, support for the use of these compounds continues from various influencers. At the cellular level, the lysosomotropic drug chloroquine accumulates in acidic organelles where it acts as an alkalizing agent with possible downstream effects on several cellular pathways. In this perspective, we discuss a possible modulatory role of these drugs in two shared features of neurodegenerative diseases, the cellular accumulation of aberrantly folded proteins and the contribution of neuroinflammation in this pathogenic process. Certainly, the decision on the use of chloroquine must be determined by its efficacy in the specific clinical situation. However, at an unprecedented time of a potential widespread use of chloroquine, we seek to raise awareness of its potential impact in ongoing clinical trials evaluating disease-modifying therapies in neurodegeneration.