TY - JOUR
T1 - Mutant huntingtin, abnormal mitochondrial dynamics, defective axonal transport of mitochondria, and selective synaptic degeneration in Huntington's disease
AU - Reddy, P. Hemachandra
AU - Shirendeb, Ulziibat P.
N1 - Funding Information:
This research was supported by NIH grants AG028072 and RR00163 , and Alzheimer Association grant IIRG-09-92429 .
PY - 2012/2
Y1 - 2012/2
N2 - Huntington'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.
AB - Huntington'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.
KW - Abnormal mitochondrial dynamics
KW - BACHD mouse
KW - Defective axonal transport
KW - Mitochondrial trafficking
KW - Mutant huntingtin
KW - RNA silencing
UR - http://www.scopus.com/inward/record.url?scp=84855165944&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84855165944&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2011.10.016
DO - 10.1016/j.bbadis.2011.10.016
M3 - Review article
C2 - 22080977
AN - SCOPUS:84855165944
SN - 0925-4439
VL - 1822
SP - 101
EP - 110
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 2
ER -