Unstable Repeat Expansion in Neurodegenerative Dementias: Mechanisms of Disease
Dementia and Neurocognitive Disorders
; : 1-12, 2012.
Article
in En
| WPRIM
| ID: wpr-133510
Responsible library:
WPRO
ABSTRACT
The majority of neurodegenerative dementias are thought to result primarily from the misfolding, aggregation and accumulation of proteins which interfere with protein homeostasis in the brain. Some of them are caused by the expansion of unstable nucleotide repeats, which include Huntington's disease as a prototype. Other neurodevelopmental or neurodegenerative disorders, such as fragile X syndrome, some spinocerebellar ataxias and myotonic dystrophies exhibit cognitive or behavioral deficits as parts of their clinical manifestations. Unstable repeat expansions include trinucleotide, tetranucleotide, and pentanucleotide. Recently hexanucleotide repeat expansion in frontotemporal dementia and amyotrophic lateral sclerosis was identified. The pathogenic mechanisms for these repeat disorders include either loss of protein function or gain of function at the protein or RNA levels. The aim of this article is to review proposed mechanisms by which unstable repeat expansions give rise to degeneration of brain with the hope of understanding the diseases and providing insights into the areas of therapeutic intervention. We will review these potential mechanisms in the context of fragile X syndrome, Huntington's disease, spinocerebellar ataxias, myotonic dystrophy, and frontotemporal dementia and amyotrophic lateral sclerosis. We will also discuss the potential targets for therapeutic intervention.
Key words
Full text:
1
Index:
WPRIM
Main subject:
Brain
/
RNA
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Proteins
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Huntington Disease
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Neurodegenerative Diseases
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Spinocerebellar Ataxias
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Dementia
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Frontotemporal Dementia
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Fragile X Syndrome
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Homeostasis
Language:
En
Journal:
Dementia and Neurocognitive Disorders
Year:
2012
Type:
Article