Abstract
Huntington's disease (HD) is an autosomal, dominantly inherited neurodegenerative disorder, characterized by chorea, involuntary movements, and cognitive impairments. Tremendous progress has been made since the discovery of HD gene in 1993, in terms of developing animal models to study the disease process, unraveling the expression and function of wild-type and mutant huntingtin (Htt) proteins in the central and peripheral nervous systems, and understanding expanded CAG repeat containing mutant Htt protein interactions with CNS proteins in the disease process. HD progression has been found to involve several pathomechanisms, including expanded CAG repeat protein interaction with other CNS proteins, transcriptional dysregulation, calcium dyshomeostasis, abnormal vesicle trafficking, and defective mitochondrial bioenergetics. Recent studies have found that mutant Htt is associated with mitochondria and causes mitochondrial structural changes, decreases mitochondrial trafficking, and impairs mitochondrial dynamics in the neurons affected by HD. This article discusses recent developments in HD research, with a particular focus on intracellular and intramitochondrial calcium influx, mitochondrial DNA defects, and mitochondrial structural and functional abnormalities in HD development and progression. Further, this article outlines the current status of mitochondrial therapeutics with a special reference to Dimebon.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 33-48 |
| Number of pages | 16 |
| Journal | Brain Research Reviews |
| Volume | 61 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jun 2009 |
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Keywords
- Calcium dyshomeostasis
- Dimebon
- Huntington's Disease
- Mitochondria
- Mitochondrial dynamics
- Polyglutamine repeat
ASJC Scopus subject areas
- Neuroscience(all)
- Clinical Neurology
Cite this
Mitochondrial structural and functional dynamics in Huntington's disease. / Reddy, P (Hemachandra); Mao, Peizhong; Manczak, Maria.
In: Brain Research Reviews, Vol. 61, No. 1, 06.2009, p. 33-48.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mitochondrial structural and functional dynamics in Huntington's disease
AU - Reddy, P (Hemachandra)
AU - Mao, Peizhong
AU - Manczak, Maria
PY - 2009/6
Y1 - 2009/6
N2 - Huntington's disease (HD) is an autosomal, dominantly inherited neurodegenerative disorder, characterized by chorea, involuntary movements, and cognitive impairments. Tremendous progress has been made since the discovery of HD gene in 1993, in terms of developing animal models to study the disease process, unraveling the expression and function of wild-type and mutant huntingtin (Htt) proteins in the central and peripheral nervous systems, and understanding expanded CAG repeat containing mutant Htt protein interactions with CNS proteins in the disease process. HD progression has been found to involve several pathomechanisms, including expanded CAG repeat protein interaction with other CNS proteins, transcriptional dysregulation, calcium dyshomeostasis, abnormal vesicle trafficking, and defective mitochondrial bioenergetics. Recent studies have found that mutant Htt is associated with mitochondria and causes mitochondrial structural changes, decreases mitochondrial trafficking, and impairs mitochondrial dynamics in the neurons affected by HD. This article discusses recent developments in HD research, with a particular focus on intracellular and intramitochondrial calcium influx, mitochondrial DNA defects, and mitochondrial structural and functional abnormalities in HD development and progression. Further, this article outlines the current status of mitochondrial therapeutics with a special reference to Dimebon.
AB - Huntington's disease (HD) is an autosomal, dominantly inherited neurodegenerative disorder, characterized by chorea, involuntary movements, and cognitive impairments. Tremendous progress has been made since the discovery of HD gene in 1993, in terms of developing animal models to study the disease process, unraveling the expression and function of wild-type and mutant huntingtin (Htt) proteins in the central and peripheral nervous systems, and understanding expanded CAG repeat containing mutant Htt protein interactions with CNS proteins in the disease process. HD progression has been found to involve several pathomechanisms, including expanded CAG repeat protein interaction with other CNS proteins, transcriptional dysregulation, calcium dyshomeostasis, abnormal vesicle trafficking, and defective mitochondrial bioenergetics. Recent studies have found that mutant Htt is associated with mitochondria and causes mitochondrial structural changes, decreases mitochondrial trafficking, and impairs mitochondrial dynamics in the neurons affected by HD. This article discusses recent developments in HD research, with a particular focus on intracellular and intramitochondrial calcium influx, mitochondrial DNA defects, and mitochondrial structural and functional abnormalities in HD development and progression. Further, this article outlines the current status of mitochondrial therapeutics with a special reference to Dimebon.
KW - Calcium dyshomeostasis
KW - Dimebon
KW - Huntington's Disease
KW - Mitochondria
KW - Mitochondrial dynamics
KW - Polyglutamine repeat
UR - http://www.scopus.com/inward/record.url?scp=67349247037&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349247037&partnerID=8YFLogxK
U2 - 10.1016/j.brainresrev.2009.04.001
DO - 10.1016/j.brainresrev.2009.04.001
M3 - Article
C2 - 19394359
AN - SCOPUS:67349247037
VL - 61
SP - 33
EP - 48
JO - Brain Research Reviews
JF - Brain Research Reviews
SN - 0165-0173
IS - 1
ER -