Title:Reviewing Biochemical Implications of Normal and Mutated Huntingtin in Huntington’s Disease
Volume: 27
Issue: 31
关键词:
亨廷顿病，亨廷顿蛋白，神经退行性病变，错误折叠，抗氧化剂，氧化应激
摘要: Huntingtin (Htt) is a multi-function protein of the brain. Normal Htt shows a common
alpha-helical structure but conformational changes in the form with beta strands are the principal
cause of Huntington’s disease. Huntington’s disease is a genetic neurological disorder caused by a
repeated expansion of the CAG trinucleotide, causing instability in the N-terminal of the gene coding
for the Huntingtin protein. The mutation leads to the abnormal expansion of the production of
the polyglutamine tract (polyQ) resulting in the form of an unstable Huntingtin protein commonly
referred to as mutant Huntingtin. Mutant Huntingtin is the cause of the complex neurological metabolic
alteration of Huntington’s disease, resulting in both the loss of all the functions of normal
Huntingtin and the genesis of abnormal interactions due to the presence of this mutation. One of the
problems arising from the misfolded Huntingtin is the increase in oxidative stress, which is common
in many neurological diseases such as Alzheimer’s, Parkinson’s, Amyotrophic Lateral Sclerosis and
Creutzfeldt-Jakob disease. In the last few years, the use of antioxidants had a strong incentive to find
valid therapies for defence against neurodegenerations. Although further studies are needed, the use
of antioxidant mixtures to counteract neuronal damages seems promising.
