HDAC6 as a potential therapeutic target for peripheral nerve disorders

Area of Science:

• Neuroscience
• Genetics
• Pharmacology

Background:

• Peripheral neuropathies involve progressive nerve dysfunction.
• Shared pathological pathways exist across various neuropathy types.
• Histone deacetylase 6 (HDAC6) is a key player in these converging pathways.

Purpose of the Study:

• To explore the role of HDAC6 in common peripheral neuropathy mechanisms.
• To review current preclinical and clinical HDAC6 inhibitors (HDAC6i).
• To discuss the development, chemical structures, and limitations of HDAC6i.

Main Methods:

• Literature review focusing on HDAC6's role in neuropathy pathogenesis.
• Analysis of existing HDAC6 inhibitor data.
• Discussion of future research directions for HDAC6i.

Main Results:

• HDAC6 activity is upregulated in neurodegenerative disorders, causing neuronal stress.
• HDAC6 influences critical pathways like axonal transport and protein degradation.
• Current HDAC6 inhibitors have limitations impacting their development.

Conclusions:

• Non-hydroxamic acid-based HDAC6 inhibitors require further development and testing.
• HDAC6 inhibitors show potential as preventative and therapeutic agents for peripheral neuropathies.