About this Research Topic
Over-accumulation or misfolding of proteins may cause their aggregation into toxic entities causing various forms of cell stress. These aggregates are the culprit of various diseases such as Tauopathies and Parkinson Disease. Carbohydrates and lipids may also respectively aggregate into malconstructed polyglucosan inclusions, causing disorders such as Lafora Disease, or into sphingolipids such as glucocerebroside fibrils causing Gaucher Disease. Treatment strategies for these macromolecule storage diseases, encompassing protein, carbohydrate and lipid overburden, are versatile and range from immunotherapy to pharmacological and gene therapy.
From all these therapeutic strategies for storage disorders, this Research Topic will focus on small molecule therapy. The importance of this topic is twofold. First, achieving a ‘pill’ that can treat a storage disorder is highly desirable due to its practicality and accessibility to a broad patient population. Therefore, it is believed that advocating small molecules as a therapeutic strategy is clinically advantageous. Secondly, it is important to broaden the perception of small molecules as a therapeutic strategy. Classically, small molecules are envisioned as molecular chaperones which assist correct folding or assembly of proteins. However, this Research Topic is aimed at broadening this concept: Small molecules act not only on protein targets. More and more works also address small molecule interactions with other macromolecules, i.e., carbohydrates and lipids. Moreover, the role of small molecules in alleviating aggregate buildup also involves stabilization of substrate breakdown enzymes, facilitation of the interaction of degradation targets with agents of the degradative pathway, such as microtubules or autophagosomes, and, in the case of proteins, inhibition of translation in order to prevent overload. Gathering mechanistic, pre-clinical, and clinical information on the usage of small molecules for the research and treatment of storage diseases will unquestionably bring us closer to finding a cure for these devastating disorders.
The use of small molecules as a therapeutic strategy for treating storage diseases is quite sporadic. In view of their potential for relatively fast and efficient bench to bed-side translation, we believe that putting together input from several experts in storage diseases and chemical biology will facilitate small molecules’ therapeutic use in storage diseases. The purpose of this article collection is to combine mechanistic and clinical information on the application of small molecules for treating storage diseases. We believe that such an issue will help to disseminate this approach, increase the awareness of it among physicians, scientists and the public, and thus lead to its application in clinical settings.
This collection welcomes articles on the mechanism of action by which small molecules can reduce toxic aggregates, as well as animal or clinical studies in which small molecules were implemented to relieve storage-related maladies. Contributions to this Research Topic may include primary basic and clinical research articles, reviews, opinion articles discussing perspectives on significant and possibly controversial topics, brief reports, and methodological studies – all related to the use of small molecules as attenuators of storage disorders.
Topic editor Pablo V. Escriba is co-founder of the company Lipopharma. All other topic editors declare no competing interests with regards to the Research Topic subject.
Keywords: small molecules, inclusion bodies, aggregates, chaperones, stress
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.