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.
Highlights
On February 4th, 2020, at the verge of a new pandemic crisis, the anti-malarial drug chloroquine (CQ), was proposed to be highly effective in controlling SARS-CoV-2 infection in vitro [1]
Food and Drug Administration (FDA) to issue an emergency use authorization (EUA) for CQ, and its analog hydroxychloroquine (HCQ), as treatments for the control of SARS-CoV-2, the severe acute respiratory syndrome caused by the new coronavirus [2]
Despite some controversy around the efficacy of CQ to penetrate the blood-brain barrier (BBB), animal studies demonstrate that this drug and its analogs can penetrate and reach a concentration that is sufficient to exert its effects within the central nervous system (CNS) [18,19,20]
Summary
On February 4th, 2020, at the verge of a new pandemic crisis, the anti-malarial drug chloroquine (CQ), was proposed to be highly effective in controlling SARS-CoV-2 infection in vitro [1]. Beside the autophagy-lysosome pathway, experimental evidence proposes that CQ is a weak antagonist of the proteasome system, causing accumulation of ubiquitinated proteins in mammalian cells [11, 12]. Despite some controversy around the efficacy of CQ to penetrate the blood-brain barrier (BBB), animal studies demonstrate that this drug and its analogs can penetrate and reach a concentration that is sufficient to exert its effects within the central nervous system (CNS) [18,19,20].
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