Mutant huntingtin, abnormal mitochondrial dynamics, defective axonal transport of mitochondria, and selective synaptic degeneration in Huntington%26apos;s disease

作者：Reddy P Hemachandra^*; Shirendeb Ulziibat P

来源：Biochimica et Biophysica Acta-Molecular Basis of Disease, 2012, 1822(2): 101-110.

DOI：10.1016/j.bbadis.2011.10.016

• Mutant huntingtin
• Abnormal mitochondrial dynamics
• Defective axonal transport
• RNA silencing
• BACHD mouse
• Mitochondrial trafficking

Huntington%26apos;s disease (HD) is a progressive, fatal neurodegenerative disease caused by expanded polyglutamine repeats in the HD gene. HD is characterized by chorea, seizures, involuntary movements, dystonia, cognitive decline, intellectual impairment and emotional disturbances. Research into mutant huntingtin (Htt) and mitochondria has found that mutant Htt interacts with the mitochondrial protein dynamin-related protein 1 (Drp1), enhances GTPase Drp1 enzymatic activity, and causes excessive mitochondrial fragmentation and abnormal distribution, leading to defective axonal transport of mitochondria and selective synaptic degeneration. This article summarizes latest developments in HD research and focuses on the role of abnormal mitochondrial dynamics and defective axonal transport in HD neurons. This article also discusses the therapeutic strategies that decrease mitochondrial fragmentation and neuronal damage in HD.

• 出版日期2012-2