he role of histone deacetylase inhibition in the accumulation and stability of disease-related proteins
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Novel treatment strategies for neurodegenerative disorders have included histone deacetylase (HDAC) inhibitors. These compounds typically act by increasing acetylation of histone proteins, leading to a relaxed chromatin state and facilitation of gene expression. However, their effects on nonhistone substrates are becoming clearer, which may also contribute to their mechanisms of action. Accumulation and aggregation of disease-causing proteins is a hallmark of several neurodegenerative disorders such as Parkinson’s, Alzheimer’s, and Huntington’s diseases. Treatment options that effectively prevent the development of misfolded and aggregated proteins in these disorders would represent an important disease-modifying therapeutic candidate. This chapter summarizes studies that have demonstrated a role of HDAC inhibitors in modulation of the expression and aggregation of several disease proteins, including huntingtin, beta-amyloid, and alpha-synuclein.