Sign up for Table of Contents Alerts.

Email this page

Print this page

Extra Views

New Directions for Neurodegenerative Disease Therapy: Using Chemical Compounds to Boost the Formation of Mutant Protein Inclusions

Ruth A. Bodner, David E. Housman and Aleksey G. Kazantsev

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.

Neurodegenerative disease such as Huntington’s, Parkinson’s, and Alzheimer’s diseases are marked by neuronal accumulation of toxic misfolded protein. Developing therapies for these misfolding diseases requires finding chemical compounds that can either clear toxic misfolded protein, or can protect neurons from their impact. Such compounds could not only provide the starting points for potential drugs, but could also provide valuable research tools for untangling the complexities of the disease process. Until now, chemical screens for these diseases have focused on finding compounds that prevent aggregation of mutant protein. We recently published a compound, B2, which promotes the formation of large inclusions by mutant Huntingtin and α-synuclein, while rescuing some of the toxic effects of these proteins. As inclusions were long believed to be toxic to cells, this contradicts previous therapeutic approaches. At the same time, the results support growing evidence for the protective effects of inclusions. In this review, we discuss these results, and place them in the context of ongoing therapeutic discovery efforts for HD and other neurodegenerative diseases.

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.